1Aderem, A & Ulevitch, RJ (2000) Toll-like receptors in the induction of the innate immune response. Nature 406, 782–787.
2Elewaut, D, DiDonato, JA, Kim, JM, et al. (1999) NF-kappa B is a central regulator of the intestinal epithelial cell innate immune response induced by infection with enteroinvasive bacteria. J Immunol 163, 1457–1466.
3Maaser, C & Kagnoff, MF (2002) Role of the intestinal epithelium in orchestrating innate and adaptive mucosal immunity. Z Gastroenterol 40, 525–529.
4Haller, D, Bode, C, Hammes, WP, et al. (2000) Non-pathogenic bacteria elicit a differential cytokine response by intestinal epithelial cell/leucocyte co-cultures. Gut 47, 79–87.
5Borruel, N, Casellas, F, Antolin, M, et al. (2003) Effects of nonpathogenic bacteria on cytokine secretion by human intestinal mucosa. Am J Gastroenterol 98, 865–870.
6Brandtzaeg, P, Farstad, IN, Johansen, FE, et al. (1999) The B-cell system of human mucosae and exocrine glands. Immunol Rev 171, 45–87.
7Shanahan, F (1994) . In Physiology of the Gastrointestinal Tract, pp. 643–684 [Johnson, LR, Christensen, J, Jacobsen, E and Walsh, JH, editors]. New York: Raven Press.
8Scott, H, Rognum, TO, Midvedt, T, et al. (1985) Age related changes of human serum antibodies to dietary and colonic bacterial antigens measured by an enzyme linked immunosorbent assay. Acta Pathol Microbiol Immunol Scand 93, 65–70.
9Brandtzaeg, PE (2002) Current understanding of gastrointestinal immunoregulation and its relation to food allergy. Ann N Y Acad Sci 964, 13–45.
10Cummings, JH, Antoine, JM, Azpiroz, F, et al. (2004) PASSCLAIM- Gut health and immunity. Eur J Nutr 43, II118–II173.
11Mulder, CJ & Cellier, C (2005) Coeliac disease: changing views. Best Pract Res Clin Gastroenterol 19, 313–321.
12Marsh, MN (1992) Gluten, major histocompatibility complex, and the small intestine. A molecular and immunobiologic approach to the spectrum of gluten sensitivity (‘celiac sprue’). Gastroenterology 102, 330–354.
13Rostom, A, Dube, C, Cranney, A, et al. (2005) The diagnostic accuracy of serologic tests for celiac disease: a systematic review. Gastroenterology 128, S38–S46.
14Rewers, M (2005) Epidemiology of celiac disease: what are the prevalence, incidence, and progression of celiac disease? Gastroenterology 128, S47–S51.
15Dube, C, Rostom, A, Sy, R, et al. (2005) The prevalence of celiac disease in average-risk and at-risk Western European populations: a systematic review. Gastroenterology 128, S57–S67.
16Liu, E, Rewers, M & Eisenbarth, GS (2005) Genetic testing: who should do the testing and what is the role of genetic testing in the setting of celiac disease? Gastroenterology 128, S33–S37.
17Ivarsson, A (2005) The Swedish epidemic of coeliac disease explored using an epidemiological approach – some lessons to be learnt. Best Pract Res Clin Gastroenterol 19, 426–440.
18Kagnoff, MF (2005) Overview and pathogenesis of celiac disease. Gastroenterology 128, S10–S18.
19Sollid, LM & Khosla, C (2005) Future therapeutic options for celiac disease. Nat Clin Pract Gastroenterol Hepatol 2, 140–147.
20Duchmann, R, Kaiser, I, Hermann, E, et al. (1995) Tolerance exists towards resident intestinal flora but is broken in active inflammatory bowel disease (IBD). Clin Exp Immunol 102, 448–455.
21Farrell, RJ & Peppercorn, MA (2002) Ulcerative colitis. Lancet 359, 331–340.
22Shanahan, F (2002) Crohn's disease. Lancet 359, 62–69.
23Carter, MJ, Lobo, AJ & Travis, SP (2004) Guidelines for the management of inflammatory bowel disease in adults. Gut 53, Suppl. 5, V1–V16.
24Ogura, Y, Bonen, DK, Inohara, N, et al. (2001) A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease. Nature 411, 603–606.
25Taurog, JD, Richardson, JA, Croft, JT, et al. (1994) The germfree state prevents development of gut and joint inflammatory disease in HLA-B27 transgenic rats. J Exp Med 180, 2359–2364.
26Macfarlane, S, Furrie, E, Kennedy, A, et al. (2005) Mucosal bacteria in ulcerative colitis. Br J Nutr 93, S67–S72.
27Furrie, E, Macfarlane, S, Kennedy, A, et al. (2005) Synbiotic therapy (Bifidobacterium longum/Synergy 1) initiates resolution of inflammation in patients with active ulcerative colitis: a randomised controlled pilot trial. Gut 54, 242–249.
28Seksik, P, Rigottier-Gois, L, Gramet, G, et al. (2003) Alterations of the dominant faecal bacterial groups in patients with Crohn's disease of the colon. Gut 52, 237–242.
29Macfarlane, S, Furrie, E, Cummings, JH, et al. (2004) Chemotaxonomic analysis of bacterial populations colonizing the rectal mucosa in patients with ulcerative colitis. Clin Infect Dis 38, 1690–1699.
30Famularo, G, Moretti, S, Marcellini, S, et al. (1997) . In Probiotics: therapeutic and Other Beneficial Effects, pp. 133–161 [Fuller, R, editor]. London: Chapman & Hall.
31Gionchetti, P, Rizzello, F, Venturi, A, et al. (2000) Oral bacteriotherapy as maintenance treatment in patients with chronic pouchitis: a double-blind, placebo-controlled trial. Gastroenterology 119, 305–309.
32Musso, A, Dentelli, P, Carlino, A, et al. (2005) Signal transducers and activators of transcription 3 signaling pathway: an essential mediator of inflammatory bowel disease and other forms of intestinal inflammation. Inflamm Bowel Dis 11, 91–98.
33von Lampe, B, Barthel, B, Coupland, SE, et al. (2000) Differential expression of matrix metalloproteinases and their tissue inhibitors in colon mucosa of patients with inflammatory bowel disease. Gut 47, 63–73.
34Rahman, I, Biswas, SK & Kode, A (2006) Oxidant and antioxidant balance in the airways and airway diseases. Eur J Pharmacol 533, 222–239.
35Hargreave, FE & Parameswaran, K (2006) Asthma, COPD and bronchitis are just components of airway disease. Eur Respir J 28, 264–267.
36Elias, J (2004) The relationship between asthma and COPD. Lessons from transgenic mice. Chest 126, 111S–116S.
37Agusti, AG, Noguera, A, Sauleda, J, et al. (2003) Systemic effects of chronic obstructive pulmonary disease. Eur Respir J 21, 347–360.
38Agusti, AG (2005) Systemic effects of chronic obstructive pulmonary disease. Proc Am Thorac Soc 2, 367–370.
39Gan, WQ, Man, SF, Senthilselvan, A, et al. (2004) Association between chronic obstructive pulmonary disease and systemic inflammation: a systematic review and a meta-analysis. Thorax 59, 574–580.
40Phipatanakul, W (2005) Allergic rhinoconjunctivitis: epidemiology. Immunol Allergy Clin North Am 25, 263–281.
41Scadding, G & Mitchell, D (2004) . In Clinical Respiratory Medicine, pp. 339–350 [Albert, RK, Spiro, SG and Jett, JR, editors]. Philadelphia, PA: Mosby.
42Strachan, D, Sibbald, B, Weiland, S, et al. (1997) Worldwide variations in prevalence of symptoms of allergic rhinoconjunctivitis in children: the International Study of Asthma and Allergies in Childhood (ISAAC). Pediatr Allergy Immunol 8, 161–176.
43Maziak, W, Behrens, T, Brasky, TM, et al. (2003) Are asthma and allergies in children and adolescents increasing? Results from ISAAC phase I and phase III surveys in Munster, Germany. Allergy 58, 572–579.
44Postma, DS, Kerstjens, HAM & Ten Hacken, NHT (2004) . In Clinical Respiratory Medicine, pp. 457–465 [Albert, RK, Spiro, SG and Jett, JR, editors]. Philadelphia, PA: Mosby.
45The International Study of Asthma and Allergies in Childhood (ISAAC) Steering Committee (1998) Worldwide variations in the prevalence of asthma symptoms: the International Study of Asthma and Allergies in Childhood (ISAAC). Eur Respir J 12, 315–335.
46The International Study of Asthma and Allergies in Childhood (ISAAC) Steering Committee (1998) Worldwide variation in prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and atopic eczema: ISAAC. Lancet 351, 1225–1232.
47Russel, G (2006) The childhood asthma epidemic. Thorax 61, 276–278.
48Zollner, IK, Weiland, SK, Piechotowski, I, et al. (2005) No increase in the prevalence of asthma, allergies, and atopic sensitisation among children in Germany: 1992–2001. Thorax 60, 545–548.
49Lodrup Carlsen, KC, Haland, G, Devulapalli, CS, et al. (2006) Asthma in every fifth child in Oslo, Norway: a 10-year follow up of a birth cohort study. Allergy 61, 454–460.
50Murray, CJ & Lopez, AD (1997) Mortality by cause for eight regions of the world: Global Burden of Disease Study. Lancet 349, 1269–1276.
51MacNee, W (2004) . In Clinical Respiratory Medicine, pp. 415–435 [Albert, RK, Spiro, SG and Jett, JR, editors]. Philadelphia, PA: Mosby.
52Leung, R & Ho, P (1994) Asthma, allergy, and atopy in three South-East Asian populations. Thorax 49, 1205–1210.
53von Mutius, E, Martinez, FD, Fritzsch, C, et al. (1994) Prevalence of asthma and atopy in two areas of West and East Germany. Am J Respir Crit Care Med 149, 358–364.
54Strachan, DP (1989) Hay fever, hygiene, and household size. BMJ 299, 1259–1260.
55Umetsu, DT (2004) Flu strikes the hygiene hypothesis. Nat Med 10, 232–234.
56Umetsu, DT (2005) Revising the immunological theories of asthma and allergy. Lancet 365, 98–100.
57Cullinan, P (2006) Childhood allergies, birth order and family size. Thorax 61, 3–5.
58von Mutius, E (2000) The environmental predictors of allergic disease. J Allergy Clin Immunol 105, 9–19.
59von Mutius, E, Martinez, FD, Fritzsch, C, et al. (1994) Skin test reactivity and number of siblings. BMJ 308, 692–695.
60Ball, TM, Castro-Rodriguez, JA, Griffith, KA, et al. (2000) Siblings, day-care attendance, and the risk of asthma and wheezing during childhood. N Engl J Med 343, 538–543.
61Riedler, J, Braun-Fahrlander, C, Eder, W, et al. (2001) Exposure to farming in early life and development of asthma and allergy: a cross-sectional survey. Lancet 358, 1129–1133.
62Floistrup, H, Swartz, J, Bergstrom, A, et al. (2006) Allergic disease and sensitization in Steiner school children. J Allergy Clin Immunol 117, 59–66.
63Platts-Mills, T, Vaughan, J, Squillace, S, et al. (2001) Sensitisation, asthma, and a modified Th2 response in children exposed to cat allergen: a population-based cross-sectional study. Lancet 357, 752–756.
64Bjorksten, B, Naaber, P, Sepp, E, et al. (1999) The intestinal microflora in allergic Estonian and Swedish 2-year-old children. Clin Exp Allergy 29, 342–346.
65McKeever, TM, Lewis, SA, Smith, C, et al. (2002) The importance of prenatal exposures on the development of allergic disease: a birth cohort study using the West Midlands General Practice Database. Am J Respir Crit Care Med 166, 827–832.
66Wong, GW, Ko, FW, Hui, DS, et al. (2004) Factors associated with difference in prevalence of asthma in children from three cities in China: multicentre epidemiological survey. BMJ 329, 486.
67Chen, R, Hu, Z & Seaton, A (2004) Eating more vegetables might explain reduced asthma symptoms. BMJ 328, 1380.
68Mickleborough, TD & Rundell, KW (2005) Dietary polyunsaturated fatty acids in asthma- and exercise-induced bronchoconstriction. Eur J Clin Nutr 59, 1335–1346.
69Beuther, DA & Sutherland, ER (2007) Overweight, obesity, and incident asthma: a meta-analysis of prospective epidemiologic studies. Am J Respir Crit Care Med 175, 661–666.
70Shaaban, R, Leynaert, B, Soussan, D, et al. (2007) Physical activity and bronchial hyperresponsiveness: European Community Respiratory Health Survey II. Thorax 62, 403–410.
71Umetsu, DT, McIntire, JJ, Akbari, O, et al. (2002) Asthma: an epidemic of dysregulated immunity. Nat Immunol 3, 715–720.
72Watson, L, Margetts, B, Howarth, P, et al. (2002) The association between diet and chronic obstructive pulmonary disease in subjects selected from general practice. Eur Respir J 20, 313–318.
73Kingma, PS & Whitsett, JA (2006) In defense of the lung: surfactant protein A and surfactant protein D. Curr Opin Pharmacol 6, 277–283.
74Van Wetering, S, Hiemstra, PS & Rabe, KF (2004) . In Clinical Respiratory Medicine, pp. 467–473 [Albert, RK, Spiro, SG and Jett, JR, editors]. Philadelphia, PA: Mosby.
75Akbari, O, Stock, P, Meyer, E, et al. (2003) Essential role of NKT cells producing IL-4 and IL-13 in the development of allergen-induced airway hyperreactivity. Nat Med 9, 582–588.
76Erin, EM, Leaker, BR, Nicholson, GC, et al. (2006) The effects of a monoclonal antibody directed against tumour necrosis factor-α (TNF-α) in asthma. Am J Respir Crit Care Med 174, 763–771.
77Ray, A & Cohn, L (1999) Th2 cells and GATA-3 in asthma: new insights into the regulation of airway inflammation. J Clin Invest 104, 985–993.
78Barrios, RJ, Kheradmand, F, Batts, L, et al. (2006) Asthma: pathology and pathophysiology. Arch Pathol Lab Med 130, 447–451.
79Steinman, L (2007) A brief history of T(H)17, the first major revision in the T(H)1/T(H)2 hypothesis of T cell-mediated tissue damage. Nat Med 13, 139–145.
80Hansen, G, Berry, G, DeKruyff, RH, et al. (1999) Allergen-specific Th1 cells fail to counterbalance Th2 cell-induced airway hyperreactivity but cause severe airway inflammation. J Clin Invest 103, 175–183.
81Randolph, DA, Carruthers, CJ, Szabo, SJ, et al. (1999) Modulation of airway inflammation by passive transfer of allergen-specific Th1 and Th2 cells in a mouse model of asthma. J Immunol 162, 2375–2383.
82Heaton, T, Rowe, J, Turner, S, et al. (2005) An immunoepidemiological approach to asthma: identification of in vitro T-cell response patterns associated with different wheezing phenotypes in children. Lancet 365, 142–149.
83Saetta, M, Di, SA, Turato, G, et al. (2005) CD8+T-lymphocytes in peripheral airways of smokers with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 157, 822–826.
84van Oosterhout, AJ & Bloksma, N (2005) Regulatory T-lymphocytes in asthma. Eur Respir J 26, 918–932.
85Finotto, S, Neurath, MF, Glickman, JN, et al. (2002) Development of spontaneous airway changes consistent with human asthma in mice lacking T-bet. Science 295, 336–338.
86Nassenstein, C, Schulte-Herbruggen, O, Renz, H, et al. (2006) Nerve growth factor: the central hub in the development of allergic asthma? Eur J Pharmacol 533, 195–206.
87De Swert, KO & Joos, GF (2006) Extending the understanding of sensory neuropeptides. Eur J Pharmacol 533, 171–181.
88Tracey, KJ (2005) Fat meets the cholinergic antiinflammatory pathway. J Exp Med 202, 1017–1021.
89Van Eerdewegh, P, Little, RD, Dupuis, J, et al. (2002) Association of the ADAM33 gene with asthma and bronchial hyperresponsiveness. Nature 418, 426–430.
90Fahy, JV, Corry, DB & Boushey, HA (2000) Airway inflammation and remodeling in asthma. Curr Opin Pulmonary Med 6, 15–20.
91Lee, KS, Park, HS, Park, SJ, et al. (2006) An antioxidant modulates expression of receptor activator of NF-kappaB in asthma. Exp Mol Med 38, 217–229.
92Fujisawa, T (2005) Role of oxygen radicals on bronchial asthma. Curr Drug Targets Inflamm Allergy 4, 505–509.
93Dworski, R (2000) Oxidant stress in asthma. Thorax 55, Suppl. 2, S51–S53.
94Chan, RC, Wang, M, Li, N, et al. (2006) Pro-oxidative diesel exhaust particle chemicals inhibit LPS-induced dendritic cell responses involved in T-helper differentiation. J Allergy Clin Immunol 118, 455–465.
95Vinzents, PS, Moller, P, Sorensen, M, et al. (2005) Personal exposure to ultrafine particles and oxidative DNA damage. Environ Health Perspect 113, 1485–1490.
96Lee, CG, Link, H, Baluk, P, et al. (2004) Vascular endothelial growth factor (VEGF) induces remodeling and enhances TH2-mediated sensitization and inflammation in the lung. Nat Med 10, 1095–1103.
97Kharitonov, SA & Barnes, PJ (2002) Biomarkers of some pulmonary diseases in exhaled breath. Biomarkers 7, 1–32.
98Kostikas, K, Papatheodorou, G, Psathakis, K, et al. (2003) Oxidative stress in expired breath condensate of patients with COPD. Chest 124, 1373–1380.
99Paredi, P, Kharitonov, SA & Barnes, PJ (2002) Analysis of expired air for oxidation products. Am J Respir Crit Care Med 166, S31–S37.
100Shapiro, SD (2003) Proteolysis in the lung. Eur Respir J Suppl 44, 30s–32s.
101D'Armiento, J, Dalal, SS, Okada, Y, et al. (1992) Collagenase expression in the lungs of transgenic mice causes pulmonary emphysema. Cell 71, 955–961.
102van Eden, W, van der Zee, R & Prakken, B (2005) Heat-shock proteins induce T-cell regulation of chronic inflammation. Nat Rev Immunol 5, 318–330.
103van Amelsfort, JM, Jacobs, KM, Bijlsma, JW, et al. (2004) CD4(+)CD25(+) regulatory T cells in rheumatoid arthritis: differences in the presence, phenotype, and function between peripheral blood and synovial fluid. Arthritis Rheum 50, 2775–2785.
104Lee, DM & Weinblatt, ME (2001) Rheumatoid arthritis. Lancet 358, 903–911.
105Pincus, T & Callahan, LF (1989) Reassessment of twelve traditional paradigms concerning the diagnosis, prevalence, morbidity and mortality of rheumatoid arthritis. Scand J Rheumatol Suppl 79, 67–96.
106Silman, AJ & Pearson, JE (2002) Epidemiology and genetics of rheumatoid arthritis. Arthritis Res 4, Suppl. 3, S265–S272.
107Uhlig, T & Kvien, TK (2005) Is rheumatoid arthritis disappearing? Ann Rheum Dis 64, 7–10.
108Woo, P & Wedderburn, LR (1998) Juvenile chronic arthritis. Lancet 351, 969–973.
109de Kleer, I, Wedderburn, LR, Taams, LS, et al. (2004) CD4+CD25bright regulatory T cells actively regulate inflammation in the joints of patients with the remitting form of juvenile idiopathic arthritis. J Immunol 172, 6435–6443.
110de Kleer, I, Kamphuis, SM, Rijkers, GT, et al. (2003) The spontaneous remission of juvenile idiopathic arthritis is characterized by CD30+T cells directed to human heat-shock protein 60 capable of producing the regulatory cytokine interleukin-10. Arthritis Rheum 48, 2001–2010.
111Nielsen, HE, Dorup, J, Herlin, T, et al. (1999) Epidemiology of juvenile chronic arthritis: risk dependent on sibship, parental income, and housing. J Rheumatol 26, 1600–1605.
112van der Helm-van Mil, AH, Wesoly, JZ & Huizinga, TW (2005) Understanding the genetic contribution to rheumatoid arthritis. Curr Opin Rheumatol 17, 299–304.
113Begovich, AB, Carlton, VE, Honigberg, LA, et al. (2004) A missense single-nucleotide polymorphism in a gene encoding a protein tyrosine phosphatase (PTPN22) is associated with rheumatoid arthritis. Am J Hum Genet 75, 330–337.
114van der Helm-van Mil, AH, Verpoort, KN, Breedveld, FC, et al. (2005) Antibodies to citrullinated proteins and differences in clinical progression of rheumatoid arthritis. Arthritis Res Ther 7, R949–R958.
115Firestein, GS (2003) Evolving concepts of rheumatoid arthritis. Nature 423, 356–361.
116Panayi, GS, Lanchbury, JS & Kingsley, GH (1992) The importance of the T cell in initiating and maintaining the chronic synovitis of rheumatoid arthritis. Arthritis Rheum 35, 729–735.
117Weyand, CM, Seyler, TM & Goronzy, JJ (2005) B cells in rheumatoid synovitis. Arthritis Res Ther 7, Suppl. 3, S9–S12.
118Bridges, SL (2004) Update on autoantibodies in rheumatoid arthritis. Curr Rheumatol Rep 6, 343–350.
119Vossenaar, ER & van Venrooij, WJ (2004) Citrullinated proteins: sparks that may ignite the fire in rheumatoid arthritis. Arthritis Res Ther 6, 107–111.
120Edwards, JC, Leandro, MJ & Cambridge, G (2004) B lymphocyte depletion therapy with rituximab in rheumatoid arthritis. Rheum Dis Clin North Am 30, 393–403.
121Firestein, GS, varo-Gracia, JM & Maki, R (1990) Quantitative analysis of cytokine gene expression in rheumatoid arthritis. J Immunol 144, 3347–3353.
122Kinne, RW, Brauer, R, Stuhlmuller, B, et al. (2000) Macrophages in rheumatoid arthritis. Arthritis Res 2, 189–202.
123Kontoyiannis, D & Kollias, G (2000) Fibroblast biology. Synovial fibroblasts in rheumatoid arthritis: leading role or chorus line? Arthritis Res 2, 342–343.
124Ehrenstein, MR, Evans, JG, Singh, A, et al. (2004) Compromised function of regulatory T cells in rheumatoid arthritis and reversal by anti-TNFalpha therapy. J Exp Med 200, 277–285.
125Williams, HC (2000) Epidemiology of atopic dermatitis. Clin Exp Dermatol 25, 522–529.
126Krutmann, J & Grewe, M (1996) Sequential activation of Th1 and Th2 cells in the immunopathogenesis of atopic eczema – the 2-phase model. Allergologie 19, 449–451.
127Thepen, T, Langeveld-Wildschut, EG, Bihari, IC, et al. (1996) Biphasic response against aeroallergen in atopic dermatitis showing a switch from an initial TH2 response to a TH1 response in situ: an immunocytochemical study. J Allergy Clin Immunol 97, 828–837.
128Saito, S (2000) Cytokine network at the feto-maternal interface. J Reprod Immunol 47, 87–103.
129von Mutius, E, Braun-Fahrlander, C, Schierl, R, et al. (2000) Exposure to endotoxin or other bacterial components might protect against the development of atopy. Clin Exp Allergy 30, 1230–1234.
130Gehring, U, Bolte, G, Borte, M, et al. (2001) Exposure to endotoxin decreases the risk of atopic eczema in infancy: a cohort study. J Allergy Clin Immunol 108, 847–854.
131Romagnani, S (2004) The increased prevalence of allergy and the hygiene hypothesis: missing immune deviation, reduced immune suppression, or both? Immunology 112, 352–363.
132Chan, SC, Kim, JW, Henderson, WR Jr, et al. (1993) Altered prostaglandin E2 regulation of cytokine production in atopic dermatitis. J Immunol 151, 3345–3352.
133Chan, S, Henderson, WR Jr, Li, SH, et al. (1996) Prostaglandin E2 control of T cell cytokine production is functionally related to the reduced lymphocyte proliferation in atopic dermatitis. J Allergy Clin Immunol 97, 85–94.
134Ena, P, Madeddu, P, Glorioso, N, et al. (1985) High prevalence of cardiovascular diseases and enhanced activity of the renin-angiotensin system in psoriatic patients. Acta Cardiol 40, 199–205.
135Rocha-Pereira, P, Santos-Silva, A, Rebelo, I, et al. (2001) Dislipidemia and oxidative stress in mild and in severe psoriasis as a risk for cardiovascular disease. Clin Chim Acta 303, 33–39.
136Bernstein, CN, Wajda, A & Blanchard, JF (2005) The clustering of other chronic inflammatory diseases in inflammatory bowel disease: a population-based study. Gastroenterology 129, 827–836.
137Allen, BR & Littlewood, SM (1983) The aetiology of psoriasis: clues provided by benoxaprofen. Br J Dermatol 109, Suppl. 25, 126–129.
138Kragballe, K & Herlin, T (1983) Benoxaprofen improves psoriasis. A double-blind study. Arch Dermatol 119, 548–552.
139Anggard, E (1994) Nitric oxide: mediator, murderer, and medicine. Lancet 343, 1199–1206.
140Penn, MS, Rangaswamy, S, Saidel, GM, et al. (1997) Macromolecular transport in the arterial intima: comparison of chronic and acute injuries. Am J Physiol 272, H1560–H1570.
141Rangaswamy, S, Penn, MS, Saidel, GM, et al. (1997) Exogenous oxidized low-density lipoprotein injures and alters the barrier function of endothelium in rats in vivo. Circ Res 80, 37–44.
142Scalia, R, Pearlman, S, Campbell, B, et al. (1996) Time course of endothelial dysfunction and neutrophil adherence and infiltration during murine traumatic shock. Shock 6, 177–182.
143Kupatt, C, Zahler, S, Seligmann, C, et al. (1996) Nitric oxide mitigates leukocyte adhesion and vascular leak after myocardial ischemia. J Mol Cell Cardiol 28, 643–654.
144Ohara, Y, Peterson, TE & Harrison, DG (1993) Hypercholesterolemia increases endothelial superoxide anion production. J Clin Invest 91, 2546–2551.
145Steinberg, D, Parthasarathy, S, Carew, TE, et al. (1989) Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity. N Engl J Med 320, 915–924.
146Miller, ER 3rd, Pastor-Barriuso, R, Dalal, D, et al. (2005) Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med 142, 37–46.
147Bjelakovic, G, Nikolova, D, Gluud, LL, et al. (2007) Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis. JAMA 297, 842–857.
148Masuda, J & Ross, R (1990) Atherogenesis during low level hypercholesterolemia in the nonhuman primate. I. Fatty streak formation. Arteriosclerosis 10, 164–177.
149Masuda, J & Ross, R (1990) Atherogenesis during low level hypercholesterolemia in the nonhuman primate. II. Fatty streak conversion to fibrous plaque. Arteriosclerosis 10, 178–187.
150Stary, HC (2000) Lipid and macrophage accumulations in arteries of children and the development of atherosclerosis. Am J Clin Nutr 72, 1297S–1306S.
151Stary, HC (2000) Natural history and histological classification of atherosclerotic lesions: an update. Arterioscler Thromb Vasc Biol 20, 1177–1178.
152Ross, R (1993) The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 362, 801–809.
153Lendon, CL, Davies, MJ, Born, GV, et al. (1991) Atherosclerotic plaque caps are locally weakened when macrophages density is increased. Atherosclerosis 87, 87–90.
154George, SJ (1998) Tissue inhibitors of metalloproteinases and metalloproteinases in atherosclerosis. Curr Opin Lipidol 9, 413–423.
155Katsuda, S, Boyd, HC, Fligner, C, et al. (1992) Human atherosclerosis. III. Immunocytochemical analysis of the cell composition of lesions of young adults. Am J Pathol 140, 907–914.
156Hansson, GK (2005) Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med 352, 1685–1695.
157Rifai, N & Ridker, PM (2002) Inflammatory markers and coronary heart disease. Curr Opin Lipidol 13, 383–389.
158Hulthe, J, Wikstrand, J & Fagerberg, B (2001) Relationship between C-reactive protein and intima-media thickness in the carotid and femoral arteries and to antibodies against oxidized low-density lipoprotein in healthy men: The Atherosclerosis and Insulin Resistance (AIR) Study. Clin Sci 100, 371–378.
159Mohamed-Ali, V & Coppack, S (2005) . In Cardiovascular Disease: Diet, Nutrition and Emerging Risk Factors, pp. 160–176 [Stanner, S, editor]. Blackwell Publishers: Oxford.
160Vaudo, G, Marchesi, S, Gerli, R, et al. (2004) Endothelial dysfunction in young patients with rheumatoid arthritis and low disease activity. Ann Rheum Dis 63, 31–35.
161Bruce, IN, Urowitz, MB, Gladman, DD, et al. (2003) Risk factors for coronary heart disease in women with systemic lupus erythematosus: The Toronto Risk Factor Study. Arthritis Rheum 48, 3159–3167.
162Kannel, WB, D'Agostino, RB, Sullivan, L, et al. (2004) Concept and usefulness of cardiovascular risk profiles. Am Heart J 148, 16–26.
163Unal, B, Critchley, JA & Capewell, S (2005) Modelling the decline in coronary heart disease deaths in England and Wales, 1981–2000: comparing contributions from primary prevention and secondary prevention. BMJ 331, 614.
164Unal, B, Critchley, JA & Capewell, S (2005) Small changes in United Kingdom cardiovascular risk factors could halve coronary heart disease mortality. J Clin Epidemiol 58, 733–740.
165Lampe, FC, Morris, RW, Walker, M, et al. (2005) Trends in rates of different forms of diagnosed coronary heart disease, 1978 to 2000: prospective, population based study of British men. BMJ 330, 1046.
166Report of the Cardiovascular Review Group, Committee on Medical Aspects of Food Policy (2004) Nutritional Aspects of Cardiovascular Disease. London: HMSO.
167Zatonski, WA & Willett, W (2005) Changes in dietary fat and declining coronary heart disease in Poland: population based study. BMJ 331, 187–188.
168British Heart Foundation Health Promotion Research Group (2003) Coronary Heart Disease Statistics. London: British Heart Foundation.
169Frayn, K & Stanner, S (2007) . In Cardiovascular Disease: Diet, Nutrition and Emerging Factors, pp. 1–21 [Stanner, S, editor]. Oxford: Blackwell Publishing.
170Baigent, C, Keech, A, Kearney, PM, et al. (2005) Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet 366, 1267–1278.
171Baigent, C, Sudlow, C, Collins, R, et al. (2002) Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 324, 71–86.
172Taylor-Robinson, D & Boman, J (2005) The failure of antibiotics to prevent heart attacks. BMJ 331, 361–362.
173Calder, PC (2006) n-3 Polyunsaturated fatty acids, inflammation, and inflammatory diseases. Am J Clin Nutr 83, 1505S–1519S.
174Thies, F, Garry, JM, Yaqoob, P, et al. (2003) Association of n-3 polyunsaturated fatty acids with stability of atherosclerotic plaques: a randomised controlled trial. Lancet 361, 477–485.
175GISSI Prevenzione (1999) Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Lancet 354, 447–455.
176Marchioli, R, Barzi, F, Bomba, E, et al. (2002) Early protection against sudden death by n-3 polyunsaturated fatty acids after myocardial infarction: time-course analysis of the results of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI)-Prevenzione. Circulation 105, 1897–1903.
177Bucher, HC, Hengstler, P, Schindler, C, et al. (2002) n-3 polyunsaturated fatty acids in coronary heart disease: a meta-analysis of randomized controlled trials. Am J Med 112, 298–304.
178Studer, M, Briel, M, Leimenstoll, B, et al. (2005) Effect of different antilipidemic agents and diets on mortality: a systematic review. Arch Intern Med 165, 725–730.
180Hutley, L & Prins, JB (2005) Fat as an endocrine organ: relationship to the metabolic syndrome. Am J Med Sci 330, 280–289.
181Fantuzzi, G (2005) Adipose tissue, adipokines, and inflammation. J Allergy Clin Immunol 115, 911–919.
182Halaas, JL, Gajiwala, KS, Maffei, M, et al. (1995) Weight-reducing effects of the plasma protein encoded by the obese gene. Science 269, 543–546.
183Montague, CT, Farooqi, IS, Whitehead, JP, et al. (1997) Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature 387, 903–908.
184Greenberg, AS & Obin, MS (2006) Obesity and the role of adipose tissue in inflammation and metabolism. Am J Clin Nutr 83, 461S–465S.
185Hotamisligil, GS, Peraldi, P, Budavari, A, et al. (1996) IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in TNF-alpha- and obesity-induced insulin resistance. Science 271, 665–668.
186Coppack, SW (2001) Pro-inflammatory cytokines and adipose tissue. Proc Nutr Soc 60, 349–356.
187Gil-Campos, M, Cañete, RR & Gil, A (2004) Adiponectin, the missing link in insulin resistance and obesity. Clin Nutr 23, 963–974.
188Hausman, DB, DiGirolamo, M, Bartness, TJ, et al. (2001) The biology of white adipocyte proliferation. Obes Rev 2, 239–254.
189Neels, JG & Olefsky, JM (2006) Inflamed fat: what starts the fire? J Clin Invest 116, 33–35.
190Unger, RH (2003) Lipid overload and overflow: metabolic trauma and the metabolic syndrome. Trends Endocrinol Metab 14, 398–403.
191Unger, RH (2003) Minireview: weapons of lean body mass destruction: the role of ectopic lipids in the metabolic syndrome. Endocrinology 144, 5159–5165.
192McGarry, JD (2002) Banting lecture 2001: dysregulation of fatty acid metabolism in the etiology of type 2 diabetes. Diabetes 51, 7–18.
193Alessi, MC, Lijnen, HR, Bastelica, D, et al. (2003) Adipose tissue and atherothrombosis. Pathophysiol Haemost Thromb 33, 290–297.
194Bougoulia, M, Triantos, A & Koliakos, G (2006) Effect of weight loss with or without orlistat treatment on adipocytokines, inflammation, and oxidative markers in obese women. Hormones (Athens) 5, 259–269.
195Cancello, R & Clement, K (2006) Is obesity an inflammatory illness? Role of low-grade inflammation and macrophage infiltration in human white adipose tissue. BJOG 113, 1141–1147.
196Zagorski, SM, Papa, NN & Chung, MH (2005) The effect of weight loss after gastric bypass on C-reactive protein levels. Surg Obes Relat Dis 1, 81–85.
197Reinehr, T, Stoffel-Wagner, B, Roth, CL, et al. (2005) High-sensitive C-reactive protein, tumor necrosis factor alpha, and cardiovascular risk factors before and after weight loss in obese children. Metabolism 54, 1155–1161.
198Hansen, EN, Torquati, A & Abumrad, NN (2006) Results of bariatric surgery. Annu Rev Nutr 26, 481–511.
199Knowler, WC, Barrett-Connor, E, Fowler, SE, et al. (2002) Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 346, 393–403.
200Tuomilehto, J, Lindstrom, J, Eriksson, JG, et al. (2001) Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 344, 1343–1350.
201Calder, PC & Burdge, GC (2004) . In Bioactive Lipids, pp. 1–36 [Nicolaou, A and Kokotos, G, editors]. Bridgewater: The Oily Press.
202Calder, PC (2001) n-3 Polyunsaturated fatty acids, inflammation and immunity: pouring oil on troubled waters or another fishy tale? Nutr Rev 21, 309–341.
203Hulshof, KF, van Erp-Baart, MA, Anttolainen, M, et al. (1999) Intake of fatty acids in western Europe with emphasis on trans fatty acids: the TRANSFAIR Study. Eur J Clin Nutr 53, 143–157.
204Burdge, GC & Calder, PC (2005) Conversion of alpha-linolenic acid to longer-chain polyunsaturated fatty acids in human adults. Reprod Nutr Dev 45, 581–597.
205Frayn, K (2003) Metabolic Regulation: A Human Perspective. Oxford: Blackwell Science.
206Lewis, RA, Austen, KF & Soberman, RJ (1990) Leukotrienes and other products of the 5-lipoxygenase pathway. Biochemistry and relation to pathobiology in human diseases. N Engl J Med 323, 645–655.
207Tilley, SL, Coffman, TM & Koller, BH (2001) Mixed messages: modulation of inflammation and immune responses by prostaglandins and thromboxanes. J Clin Invest 108, 15–23.
208Kelley, DS, Taylor, PC, Nelson, GJ, et al. (1998) Arachidonic acid supplementation enhances synthesis of eicosanoids without suppressing immune functions in young healthy men. Lipids 33, 125–130.
209Thies, F, Miles, EA, Nebe-von-Caron, G, et al. (2001) Influence of dietary supplementation with long-chain n-3 or n-6 polyunsaturated fatty acids on blood inflammatory cell populations and functions and on plasma soluble adhesion molecules in healthy adults. Lipids 36, 1183–1193.
210Healy, DA, Wallace, FA, Miles, EA, et al. (2000) Effect of low-to-moderate amounts of dietary fish oil on neutrophil lipid composition and function. Lipids 35, 763–768.
211Rees, D, Miles, EA, Banerjee, T, et al. (2006) Dose-related effects of eicosapentaenoic acid on innate immune function in healthy humans: a comparison of young and older men. Am J Clin Nutr 83, 331–342.
212Kelley, DS, Taylor, PC, Nelson, GJ, et al. (1999) Docosahexaenoic acid ingestion inhibits natural killer cell activity and production of inflammatory mediators in young healthy men. Lipids 34, 317–324.
213Serhan, CN, Arita, M, Hong, S, et al. (2004) Resolvins, docosatrienes, and neuroprotectins, novel omega-3-derived mediators, and their endogenous aspirin-triggered epimers. Lipids 39, 1125–1132.
214Serhan, CN (2005) Novel eicosanoid and docosanoid mediators: resolvins, docosatrienes, and neuroprotectins. Curr Opin Clin Nutr Metab Care 8, 115–121.
215Hughes, DA, Pinder, AC, Piper, Z, et al. (1996) Fish oil supplementation inhibits the expression of major histocompatibility complex class II molecules and adhesion molecules on human monocytes. Am J Clin Nutr 63, 267–272.
216Miles, EA, Thies, F, Wallace, FA, et al. (2001) Influence of age and dietary fish oil on plasma soluble adhesion molecule concentrations. Clin Sci 100, 91–100.
217Caughey, GE, Mantzioris, E, Gibson, RA, et al. (1996) The effect on human tumor necrosis factor alpha and interleukin 1 beta production of diets enriched in n-3 fatty acids from vegetable oil or fish oil. Am J Clin Nutr 63, 116–122.
218Mori, TA, Woodman, RJ, Burke, V, et al. (2003) Effect of eicosapentaenoic acid and docosahexaenoic acid on oxidative stress and inflammatory markers in treated-hypertensive type 2 diabetic subjects. Free Radic Biol Med 35, 772–781.
219Burdge, GC & Calder, PC (2006) Dietary α-linolenic acid and health-related outcomes: a metabolic perspective. Nutr Res Rev 19, 26–52.
220Lopez-Garcia, E, Schulze, MB, Fung, TT, et al. (2004) Major dietary patterns are related to plasma concentrations of markers of inflammation and endothelial dysfunction. Am J Clin Nutr 80, 1029–1035.
221Rallidis, LS, Paschos, G, Papaioannou, ML, et al. (2004) The effect of diet enriched with alpha-linolenic acid on soluble cellular adhesion molecules in dyslipidaemic patients. Atherosclerosis 174, 127–132.
222Bemelmans, WJ, Lefrandt, JD, Feskens, EJ, et al. (2004) Increased alpha-linolenic acid intake lowers C-reactive protein, but has no effect on markers of atherosclerosis. Eur J Clin Nutr 58, 1083–1089.
223Rallidis, LS, Paschos, G, Liakos, GK, et al. (2003) Dietary alpha-linolenic acid decreases C-reactive protein, serum amyloid A and interleukin-6 in dyslipidaemic patients. Atherosclerosis 167, 237–242.
224Zhao, G, Etherton, TD, Martin, KR, et al. (2004) Dietary alpha-linolenic acid reduces inflammatory and lipid cardiovascular risk factors in hypercholesterolemic men and women. J Nutr 134, 2991–2997.
225Arita, M, Yoshida, M, Hong, S, et al. (2005) Resolvin E1, an endogenous lipid mediator derived from omega-3 eicosapentaenoic acid, protects against 2,4,6-trinitrobenzene sulfonic acid-induced colitis. Proc Natl Acad Sci U S A 102, 7671–7676.
226Calder, PC (2003) n-3 Polyunsaturated fatty acids and inflammation: from molecular biology to the clinic. Lipids 38, 342–352.
227Calder, PC (2004) n-3 fatty acids, inflammation, and immunity – relevance to postsurgical and critically ill patients. Lipids 39, 1147–1161.
228Lee, JY, Plakidas, A, Lee, WH, et al. (2003) Differential modulation of Toll-like receptors by fatty acids: preferential inhibition by n-3 polyunsaturated fatty acids. J Lipid Res 44, 479–486.
229Lee, JY, Ye, J, Gao, Z, et al. (2003) Reciprocal modulation of Toll-like receptor-4 signaling pathways involving MyD88 and phosphatidylinositol 3-kinase/AKT by saturated and polyunsaturated fatty acids. J Biol Chem 278, 37041–37051.
230Lee, JY, Zhao, L, Youn, HS, et al. (2004) Saturated fatty acid activates but polyunsaturated fatty acid inhibits Toll-like receptor 2 dimerized with Toll-like receptor 6 or 1. J Biol Chem 279, 16971–16979.
231Weatherill, AR, Lee, JY, Zhao, L, et al. (2005) Saturated and polyunsaturated fatty acids reciprocally modulate dendritic cell functions mediated through TLR4. J Immunol 174, 5390–5397.
232Shoda, R, Matsueda, K, Yamato, S, et al. (1996) Epidemiologic analysis of Crohn disease in Japan: increased dietary intake of n-6 polyunsaturated fatty acids and animal protein relates to the increased incidence of Crohn disease in Japan. Am J Clin Nutr 63, 741–745.
233Belluzzi, A, Brignola, C, Campieri, M, et al. (1996) Effect of an enteric-coated fish-oil preparation on relapses in Crohn's disease. N Engl J Med 334, 1557–1560.
234MacLean, CH, Mojica, WA, Morton, SC, et al. (2004) Effects of Omega-3 Fatty Acids on Inflammatory Bowel Disease, Rheumatoid Arthritis, Renal Disease, Systemic Lupus Erythematosus, and Osteoporosis. Rockville, IN: Agency for Healthcare Research and Quality.
235Dunstan, JA, Mori, TA, Barden, A, et al. (2003) Maternal fish oil supplementation in pregnancy reduces interleukin-13 levels in cord blood of infants at high risk of atopy. Clin Exp Allergy 33, 442–448.
236Dunstan, JA, Mori, TA, Barden, A, et al. (2003) Fish oil supplementation in pregnancy modifies neonatal allergen-specific immune responses and clinical outcomes in infants at high risk of atopy: a randomized, controlled trial. J Allergy Clin Immunol 112, 1178–1184.
237Thien, FCK, Woods, R, De Luca, S, et al. (2002) .
238Nagakura, T, Matsuda, S, Shichijyo, K, et al. (2000) Dietary supplementation with fish oil rich in omega-3 polyunsaturated fatty acids in children with bronchial asthma. Eur Respir J 16, 861–865.
239Schachter, H, Reisman, J, Tran, K, et al. (2004) Health Effects of Omega-3 Fatty Acids on Asthma. Rockville, IN: Agency for Healthcare and Quality.
240Broughton, KS, Johnson, CS, Pace, BK, et al. (1997) Reduced asthma symptoms with n-3 fatty acid ingestion are related to 5-series leukotriene production. Am J Clin Nutr 65, 1011–1017.
241Broekhuizen, R, Wouters, EF, Creutzberg, EC, et al. (2005) Polyunsaturated fatty acids improve exercise capacity in chronic obstructive pulmonary disease. Thorax 60, 376–382.
242Matsuyama, W, Mitsuyama, H, Watanabe, M, et al. (2005) Effects of omega-3 polyunsaturated fatty acids on inflammatory markers in COPD. Chest 128, 3817–3827.
243Adam, O, Beringer, C, Kless, T, et al. (2003) Anti-inflammatory effects of a low arachidonic acid diet and fish oil in patients with rheumatoid arthritis. Rheumatol Int 23, 27–36.
244Fortin, PR, Lew, RA, Liang, MH, et al. (1995) Validation of a meta-analysis: the effects of fish oil in rheumatoid arthritis. J Clin Epidemiol 48, 1379–1390.
245Mayser, P, Mrowietz, U, Arenberger, P, et al. (1998) Omega-3 fatty acid-based lipid infusion in patients with chronic plaque psoriasis: results of a double-blind, randomized, placebo-controlled, multicenter trial. J Am Acad Dermatol 38, 539–547.
246Ziboh, V (1998) . In Medicinal Fatty Acids in Inflammation, pp. 45–53 [Kremer, J, editor]. Basel: Birkhauser Verlag.
247Rhodes, LE, O'Farrell, S, Jackson, MJ, et al. (1994) Dietary fish oil supplementation in humans reduces UVB-erythemal sensitivity but increases epidermal lipid peroxidation. J Invest Dermatol 103, 151–154.
248Rhodes, LE, Durham, B, Fraser, W, et al. (1994) Fish oil reduces PGE2 levels in skin and increases the threshold to provocation of polymorphic light eruption. J Invest Dermatol 103, 404.
249Kris-Etherton, PM, Harris, WS & Appel, LJ (2002) Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation 106, 2747–2757.
250Calder, PC (2004) n-3 Fatty acids and cardiovascular disease: evidence explained and mechanisms explored. Clin Sci 107, 1–11.
251Serafini, M & Del, RD (2004) Understanding the association between dietary antioxidants, redox status and disease: is the Total Antioxidant Capacity the right tool? Redox Rep 9, 145–152.
252Serafini, M, Bugianesi, R, Maiani, G, et al. (2003) Plasma antioxidants from chocolate. Nature 424, 1013.
253Vassalle, C, Petrozzi, L, Botto, N, et al. (2004) Oxidative stress and its association with coronary artery disease and different atherogenic risk factors. J Intern Med 256, 308–315.
254Ching, S, Ingram, D, Hahnel, R, et al. (2002) Serum levels of micronutrients, antioxidants and total antioxidant status predict risk of breast cancer in a case control study. J Nutr 132, 303–306.
255Serafini, M, Bellocco, R, Wolk, A, et al. (2002) Total antioxidant potential of fruit and vegetables and risk of gastric cancer. Gastroenterology 123, 985–991.
256Agudo, A, Cabrera, L, Amiano, P, et al. (2007) Fruit and vegetable intakes, dietary antioxidant nutrients, and total mortality in Spanish adults: findings from the Spanish cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Spain). Am J Clin Nutr 85, 1634–1642.
257Brighenti, F, Valtuena, S, Pellegrini, N, et al. (2005) Total antioxidant capacity of the diet is inversely and independently related to plasma concentration of high-sensitivity C-reactive protein in adult Italian subjects. Br J Nutr 93, 619–625.
258Food and Nutrition Board IoM (2000) Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium and Carotenoids. Washington.
259Levine, M, Conry-Cantilena, C, Wang, Y, et al. (1996) Vitamin C pharmacokinetics in healthy volunteers: evidence for a recommended dietary allowance. Proc Natl Acad Sci U S A 93, 3704–3709.
260Frei, B, England, L & Ames, BN (1989) Ascorbate is an outstanding antioxidant in human blood plasma. Proc Natl Acad Sci U S A 86, 6377–6381.
261Levine, M, Dhariwal, KR, Wang, Y, et al. (1994) . In Natural Antioxidants in Health and Disease, pp. 469–488 [Frei, B, editor]. San Diego, CA: Academic Press.
262Frei, B, Stocker, R & Ames, BN (1988) Antioxidant defenses and lipid peroxidation in human blood plasma. Proc Natl Acad Sci U S A 85, 9748–9752.
263Jialal, I, Vega, GL & Grundy, SM (1990) Physiologic levels of ascorbate inhibit the oxidative modification of low density lipoprotein. Atherosclerosis 82, 185–191.
264Halpner, AD, Handelman, GJ, Belmont, CA, et al. (1998) Protection by vitamin C of oxidant-induced loss of vitamin E in rat hepatocytes. J Nutr Biochem 9, 355–359.
265Horrobin, DF (1996) Ascorbic acid and prostaglandin synthesis. Subcell Biochem 25, 109–115.
266Halliwell, B, Wasil, M & Grootveld, M (1987) Biologically significant scavenging of the myeloperoxidase-derived oxidant hypochlorous acid by ascorbic acid. Implications for antioxidant protection in the inflamed rheumatoid joint. FEBS Lett 213, 15–17.
267Anderson, R & Lukey, PT (1987) A biological role for ascorbate in the selective neutralization of extracellular phagocyte-derived oxidants. Ann N Y Acad Sci 498, 229–247.
268Goetzl, EJ, Wasserman, SI, Gigli, I, et al. (1974) Enhancement of random migration and chemotactic response of human leukocytes by ascorbic acid. J Clin Invest 53, 813–818.
269Sanchez-Moreno, C, Cano, MP, de Ancos, B, et al. (2004) Consumption of high-pressurized vegetable soup increases plasma vitamin C and decreases oxidative stress and inflammatory biomarkers in healthy humans. J Nutr 134, 3021–3025.
270Sanchez-Moreno, C, Dashe, JF, Scott, T, et al. (2004) Decreased levels of plasma vitamin C and increased concentrations of inflammatory and oxidative stress markers after stroke. Stroke 35, 163–168.
271Evans, RM, Currie, L & Campbell, A (1982) The distribution of ascorbic acid between various cellular components of blood, in normal individuals, and its relation to the plasma concentration. Br J Nutr 47, 473–482.
272Lunec, J & Blake, DR (1985) The determination of dehydroascorbic acid and ascorbic acid in the serum and synovial fluid of patients with rheumatoid arthritis (RA). Free Radic Res Commun 1, 31–39.
273Cross, CE, Forte, T, Stocker, R, et al. (1990) Oxidative stress and abnormal cholesterol metabolism in patients with adult respiratory distress syndrome. J Lab Clin Med 115, 396–404.
274Imes, S, Dinwoodie, A, Walker, K, et al. (1986) Vitamin C status in 137 outpatients with Crohn's disease. Effect of diet counseling. J Clin Gastroenterol 8, 443–446.
275Hoffenberg, EJ, Deutsch, J, Smith, S, et al. (1997) Circulating antioxidant concentrations in children with inflammatory bowel disease. Am J Clin Nutr 65, 1482–1488.
276Filippi, J, Al-Jaouni, R, Wiroth, JB, et al. (2006) Nutritional deficiencies in patients with Crohn's disease in remission. Inflamm Bowel Dis 12, 185–191.
277Wendland, BE, Aghdassi, E, Tam, C, et al. (2001) Lipid peroxidation and plasma antioxidant micronutrients in Crohn disease. Am J Clin Nutr 74, 259–264.
278Buffinton, GD & Doe, WF (1995) Altered ascorbic acid status in the mucosa from inflammatory bowel disease patients. Free Radic Res 22, 131–143.
279Aghdassi, E, Wendland, BE, Steinhart, AH, et al. (2003) Antioxidant vitamin supplementation in Crohn's disease decreases oxidative stress. a randomized controlled trial. Am J Gastroenterol 98, 348–353.
280Trebble, TM, Arden, NK, Wootton, SA, et al. (2004) Fish oil and antioxidants alter the composition and function of circulating mononuclear cells in Crohn disease. Am J Clin Nutr 80, 1137–1144.
281Kelly, FJ, Mudway, I, Blomberg, A, et al. (1999) Altered lung antioxidant status in patients with mild asthma. Lancet 354, 482–483.
282Winklhofer-Roob, BM, Ellemunter, H, Fruhwirth, M, et al. (1997) Plasma vitamin C concentrations in patients with cystic fibrosis: evidence of associations with lung inflammation. Am J Clin Nutr 65, 1858–1866.
283Schwartz, J & Weiss, ST (1994) Relationship between dietary vitamin C intake and pulmonary function in the First National Health and Nutrition Examination Survey (NHANES I). Am J Clin Nutr 59, 110–114.
284Britton, JR, Pavord, ID, Richards, KA, et al. (1995) Dietary antioxidant vitamin intake and lung function in the general population. Am J Respir Crit Care Med 151, 1383–1387.
285Harik-Khan, RI, Muller, DC & Wise, RA (2004) Serum vitamin levels and the risk of asthma in children. Am J Epidemiol 159, 351–357.
286Devereux, G, Turner, SW, Craig, LC, et al. (2006) Low maternal vitamin E intake during pregnancy is associated with asthma in 5-year-old children. Am J Respir Crit Care Med 174, 499–507.
287Aderele, WI, Ette, SI, Oduwole, O, et al. (1985) Plasma vitamin C (ascorbic acid) levels in asthmatic children. Afr J Med Med Sci 14, 115–120.
288Bucca, C, Rolla, G & Farina, JC (1992) Effect of vitamin C on transient increase of bronchial responsiveness in conditions affecting the airways. Ann N Y Acad Sci 669, 175–186.
289Cohen, HA, Neuman, I & Nahum, H (1997) Blocking effect of vitamin C in exercise-induced asthma. Arch Pediatr Adolesc Med 151, 367–370.
290Tecklenburg, SL, Mickleborough, TD, Fly, AD, et al. (2007) Ascorbic acid supplementation attenuates exercise-induced bronchoconstriction in patients with asthma. Respir Med 101, 1770–1778.
291Hagfors, L, Leanderson, P, Skoldstam, L, et al. (2003) Antioxidant intake, plasma antioxidants and oxidative stress in a randomized, controlled, parallel, Mediterranean dietary intervention study on patients with rheumatoid arthritis. Nutr J 2, 5.
292Traber, MG (2007) Heart disease and single-vitamin supplementation. Am J Clin Nutr 85, 293S–299S.
293van Herpen-Broekmans, WM, Klopping-Ketelaars, IA, Bots, ML, et al. (2004) Serum carotenoids and vitamins in relation to markers of endothelial function and inflammation. Eur J Epidemiol 19, 915–921.
294Plantinga, Y, Ghiadoni, L, Magagna, A, et al. (2007) Supplementation with vitamins C and E improves arterial stiffness and endothelial function in essential hypertensive patients. Am J Hypertens 20, 392–397.
295Tahir, M, Foley, B, Pate, G, et al. (2005) Impact of vitamin E and C supplementation on serum adhesion molecules in chronic degenerative aortic stenosis: a randomized controlled trial. Am Heart J 150, 302–306.
296Traber, MG, Burton, GW, Ingold, KU, et al. (1990) RRR- and SRR-alpha-tocopherols are secreted without discrimination in human chylomicrons, but RRR-alpha-tocopherol is preferentially secreted in very low density lipoproteins. J Lipid Res 31, 675–685.
297Schultz, M, Leist, M, Elsner, A, et al. (1997) Alpha-carboxyethyl-6-hydroxychroman as urinary metabolite of vitamin E. Methods Enzymol 282, 297–310.
298Lodge, JK, Ridlington, J, Leonard, S, et al. (2001) Alpha- and gamma-tocotrienols are metabolized to carboxyethyl-hydroxychroman derivatives and excreted in human urine. Lipids 36, 43–48.
299McLaughlin, PJ & Weihrauch, JL (1979) Vitamin E content of foods. J Am Diet Assoc 75, 647–665.
300Lehmann, J, Martin, HL, Lashley, EL, et al. (1986) Vitamin E in foods from high and low linoleic acid diets. J Am Diet Assoc 86, 1208–1216.
301Murphy, SP, Subar, AF & Block, G (1990) Vitamin E intakes and sources in the United States. Am J Clin Nutr 52, 361–367.
302Slesinski, MJ, Subar, AF & Kahle, LL (1996) Dietary intake of fat, fiber and other nutrients is related to the use of vitamin and mineral supplements in the United States: the 1992 National Health Interview Survey. J Nutr 126, 3001–3008.
303Burton, GW & Ingold, KU (1986) Vitamin E: Application of the principles of physical organic chemistry to the exploration of its structure and functions. Acc Chem Rec 19, 194–201.
304Kamal-Eldin, A & Appelqvist, LA (1996) The chemistry and antioxidant properties of tocopherols and tocotrienols. Lipids 31, 671–701.
305Jiang, Q, Christen, S, Shigenaga, MK, et al. (2001) Gamma-tocopherol, the major form of vitamin E in the US diet, deserves more attention. Am J Clin Nutr 74, 714–722.
306Winklhofer-Roob, BM, Rock, E, Ribalta, J, et al. (2003) Effects of vitamin E and carotenoid status on oxidative stress in health and disease. Evidence obtained from human intervention studies. Mol Aspects Med 24, 391–402.
307Winklhofer-Roob, BM, Ziouzenkova, O, Puhl, H, et al. (1995) Impaired resistance to oxidation of low density lipoprotein in cystic fibrosis: improvement during vitamin E supplementation. Free Radic Biol Med 19, 725–733.
308Saldeen, T, Li, D & Mehta, JL (1999) Differential effects of alpha- and gamma-tocopherol on low-density lipoprotein oxidation, superoxide activity, platelet aggregation and arterial thrombogenesis. J Am Coll Cardiol 34, 1208–1215.
309Liu, M, Wallin, R, Wallmon, A, et al. (2002) Mixed tocopherols have a stronger inhibitory effect on lipid peroxidation than alpha-tocopherol alone. J Cardiovasc Pharmacol 39, 714–721.
310Devaraj, S, Hugou, I & Jialal, I (2001) Alpha-tocopherol decreases CD36 expression in human monocyte-derived macrophages. J Lipid Res 42, 521–527.
311Bieri, JG & Evarts, RP (1974) Vitamin E activity of gamma-tocopherol in the rat, chick and hamster. J Nutr 104, 850–857.
312Cooney, RV, Franke, AA, Harwood, PJ, et al. (1993) Gamma-tocopherol detoxification of nitrogen dioxide: superiority to alpha-tocopherol. Proc Natl Acad Sci U S A 90, 1771–1775.
313Christen, S, Woodall, AA, Shigenaga, MK, et al. (1997) Gamma-tocopherol traps mutagenic electrophiles such as NO(X) and complements alpha-tocopherol: physiological implications. Proc Natl Acad Sci U S A 94, 3217–3222.
314Devaraj, S & Jialal, I (2000) Alpha tocopherol supplementation decreases serum C-reactive protein and monocyte interleukin-6 levels in normal volunteers and type 2 diabetic patients. Free Radic Biol Med 29, 790–792.
315Sundl, I, Gruber, HJ & Roob, JM (2005) Effects of mixed tocopherols versus alpha-tocopherol on nuclear factor kappa B activation in mononuclear leukocytes of healthy male volunteers. Clin Nutr 24, 595.
316Tasinato, A, Boscoboinik, D, Bartoli, GM, et al. (1995) d-alpha-tocopherol inhibition of vascular smooth muscle cell proliferation occurs at physiological concentrations, correlates with protein kinase C inhibition, and is independent of its antioxidant properties. Proc Natl Acad Sci U S A 92, 12190–12194.
317Devaraj, S & Jialal, I (1999) Alpha-tocopherol decreases interleukin-1 beta release from activated human monocytes by inhibition of 5-lipoxygenase. Arterioscler Thromb Vasc Biol 19, 1125–1133.
318Jiang, Q, Lykkesfeldt, J, Shigenaga, MK, et al. (2002) Gamma-tocopherol supplementation inhibits protein nitration and ascorbate oxidation in rats with inflammation. Free Radic Biol Med 33, 1534–1542.
319Grammas, P, Hamdheydari, L, Benaksas, EJ, et al. (2004) Anti-inflammatory effects of tocopherol metabolites. Biochem Biophys Res Commun 319, 1047–1052.
320Jiang, Q & Ames, BN (2003) Gamma-tocopherol, but not alpha-tocopherol, decreases proinflammatory eicosanoids and inflammation damage in rats. FASEB J 17, 816–822.
321Li, D, Saldeen, T & Mehta, JL (1999) Gamma-tocopherol decreases ox-LDL-mediated activation of nuclear factor-kappaB and apoptosis in human coronary artery endothelial cells. Biochem Biophys Res Commun 259, 157–161.
322Jiang, Q, Elson-Schwab, I, Courtemanche, C, et al. (2000) Gamma-tocopherol and its major metabolite, in contrast to alpha-tocopherol, inhibit cyclooxygenase activity in macrophages and epithelial cells. Proc Natl Acad Sci U S A 97, 11494–11499.
323Heliovaara, M, Knekt, P, Aho, K, et al. (1994) Serum antioxidants and risk of rheumatoid arthritis. Ann Rheum Dis 53, 51–53.
324De Bandt, M, Grossin, M, Driss, F, et al. (2002) Vitamin E uncouples joint destruction and clinical inflammation in a transgenetic mouse model of rheumatoid arthritis. Arthritis Rheum 46, 522–532.
325Venkatraman, JT & Chu, WC (1999) Effects of dietary omega-3 and omega-6 lipids and vitamin E on serum cytokines, lipid mediators and anti-DNA antibodies in a mouse model for rheumatoid arthritis. J Am Coll Nutr 18, 602–613.
326Edmonds, SE, Winyard, PG, Guo, R, et al. (1997) Putative analgesic activity of repeated oral doses of vitamin E in the treatment of rheumatoid arthritis. Results of a prospective placebo controlled double blind trial. Ann Rheum Dis 56, 649–655.
327Dieber-Rotheneder, M, Puhl, H, Waeg, G, et al. (1991) Effect of oral supplementation with d-alpha-tocopherol on the vitamin E content of human low density lipoproteins and resistance to oxidation. J Lipid Res 32, 1325–1332.
328Steinbrecher, UP, Parthasarathy, S, Leake, DS, et al. (1984) Modification of low density lipoprotein by endothelial cells involves lipid peroxidation and degradation of low density lipoprotein phospholipids. Proc Natl Acad Sci U S A 81, 3883–3887.
329Azzi, A, Boscoboinik, D & Marilley, D (1995) Vitamin E: a sensor and an information transducer of the cell oxidation state. Am J Clin Nutr 62, 1337S–1346S.
330Freedman, JE, Farhat, JH, Loscalzo, J, et al. (1996) Alpha-tocopherol inhibits aggregation of human platelets by a protein kinase C-dependent mechanism. Circulation 94, 2434–2440.
331Devaraj, S, Li, D & Jialal, I (1996) The effects of alpha tocopherol supplementation on monocyte function. Decreased lipid oxidation, interleukin 1 beta secretion, and monocyte adhesion to endothelium. J Clin Invest 98, 756–763.
332Chan, AC & Leith, MK (1981) Decreased prostacyclin synthesis in vitamin E-deficient rabbit aorta. Am J Clin Nutr 34, 2341–2347.
333Tran, K & Chan, AC (1990) R,R,R-alpha-tocopherol potentiates prostacyclin release in human endothelial cells. Evidence for structural specificity of the tocopherol molecule. Biochim Biophys Acta 1043, 189–197.
334Chan, AC, Wagner, M, Kennedy, C, et al. (1998) Vitamin E up-regulates arachidonic acid release and phospholipase A2 in megakaryocytes. Mol Cell Biochem 189, 153–159.
335Cominacini, L, Garbin, U, Pasini, AF, et al. (1997) Antioxidants inhibit the expression of intercellular cell adhesion molecule-1 and vascular cell adhesion molecule-1 induced by oxidized LDL on human umbilical vein endothelial cells. Free Radic Biol Med 22, 117–127.
336Ohrvall, M, Sundlof, G & Vessby, B (1996) Gamma, but not alpha, tocopherol levels in serum are reduced in coronary heart disease patients. J Intern Med 239, 111–117.
337Handelman, GJ, Machlin, LJ, Fitch, K, et al. (1985) Oral alpha-tocopherol supplements decrease plasma gamma-tocopherol levels in humans. J Nutr 115, 807–813.
338Sundl, I, Resch, U, Bergmann, AR, et al. (2004) The decrease in gamma-tocopherol in plasma and lipoprotein fractions levels off within two days of vitamin E supplementation. Ann N Y Acad Sci 1031, 378–380.
339Drewnowski, A, Rock, CL, Henderson, SA, et al. (1997) Serum beta-carotene and vitamin C as biomarkers of vegetable and fruit intakes in a community-based sample of French adults. Am J Clin Nutr 65, 1796–1802.
340Krinsky, NI (1993) Actions of carotenoids in biological systems. Annu Rev Nutr 13, 561–587.
341Krinsky, NI (2002) Possible biologic mechanisms for a protective role of xanthophylls. J Nutr 132, 540S–542S.
342Bai, SK, Lee, SJ, Na, HJ, et al. (2005) beta-Carotene inhibits inflammatory gene expression in lipopolysaccharide-stimulated macrophages by suppressing redox-based NF-kappaB activation. Exp Mol Med 37, 323–334.
343Flohé, L, Brigelius-Flohé, R, Saliou, C, et al. (1997) Redox regulation of NF-kB activation. Free Radic Biol Med 22, 1115–1126.
344Louw, JA, Werbeck, A, Louw, ME, et al. (1992) Blood vitamin concentrations during the acute-phase response. Crit Care Med 20, 934–941.
345Kritchevsky, SB, Bush, AJ, Pahor, M, et al. (2000) Serum carotenoids and markers of inflammation in nonsmokers. Am J Epidemiol 152, 1065–1071.
346Quasim, T, McMillan, DC, Talwar, D, et al. (2003) Lower concentrations of carotenoids in the critically ill patient are related to a systemic inflammatory response and increased lipid peroxidation. Clin Nutr 22, 459–462.
347Lakshman, MR & Rao, MN (1999) Purification and characterization of cellular carotenoid-binding protein from mammalian liver. Methods Enzymol 299, 441–456.
348Kim, GY, Kim, JH, Ahn, SC, et al. (2004) Lycopene suppresses the lipopolysaccharide-induced phenotypic and functional maturation of murine dendritic cells through inhibition of mitogen-activated protein kinases and nuclear factor-kappaB. Immunology 113, 203–211.
349Ohgami, K, Shiratori, K, Kotake, S, et al. (2003) Effects of astaxanthin on lipopolysaccharide-induced inflammation in vitro and in vivo. Invest Ophthalmol Vis Sci 44, 2694–2701.
350Lee, EH, Faulhaber, D, Hanson, KM, et al. (2004) Dietary lutein reduces ultraviolet radiation-induced inflammation and immunosuppression. J Invest Dermatol 122, 510–517.
351Watzl, B, Kulling, SE, Möseneder, J, et al. (2005) A 4-week intervention with high intake of carotenoid-rich vegetables and fruit reduces plasma C-reactive protein in healthy, non-smoking men. Am J Clin Nutr 82, 1052–1058.
352Riso, P, Visioli, F, Grande, S, et al. (2006) Effect of a tomato-based drink on markers of inflammation, immunomodulation, and oxidative stress. J Agric Food Chem 54, 2563–2566.
353Rumi, G Jr, Szabo, I, Vincze, A, et al. (2000) Decrease of serum carotenoids in Crohn's disease. J Physiol Paris 94, 159–161.
354Reifen, R, Nur, T, Matas, Z, et al. (2001) Lycopene supplementation attenuates the inflammatory status of colitis in a rat model. Int J Vitam Nutr Res 71, 347–351.
355Wood, LG, Garg, ML, Blake, RJ, et al. (2004) Carotenoid concentrations in asthmatics versus healthy controls. Asia Pac J Clin Nutr 13, S74.
356Cerhan, JR, Saag, KG, Merlino, LA, et al. (2003) Antioxidant micronutrients and risk of rheumatoid arthritis in a cohort of older women. Am J Epidemiol 157, 345–354.
357Pattison, DJ, Symmons, DP, Lunt, M, et al. (2005) Dietary beta-cryptoxanthin and inflammatory polyarthritis: results from a population-based prospective study. Am J Clin Nutr 82, 451–455.
358Comstock, GW, Burke, AE, Hoffman, SC, et al. (1997) Serum concentrations of alpha tocopherol, beta carotene, and retinol preceding the diagnosis of rheumatoid arthritis and systemic lupus erythematosus. Ann Rheum Dis 56, 323–325.
359Sesso, HD, Buring, JE, Norkus, EP, et al. (2004) Plasma lycopene, other carotenoids, and retinol and the risk of cardiovascular disease in women. Am J Clin Nutr 79, 47–53.
360Sesso, HD, Buring, JE, Norkus, EP, et al. (2005) Plasma lycopene, other carotenoids, and retinol and the risk of cardiovascular disease in men. Am J Clin Nutr 81, 990–997.
361Suzuki, K, Inoue, T, Hioki, R, et al. (2006) Association of abdominal obesity with decreased serum levels of carotenoids in a healthy Japanese population. Clin Nutr 25, 780–789.
362Wallstrom, P, Wirfalt, E, Lahmann, PH, et al. (2001) Serum concentrations of beta-carotene and alpha-tocopherol are associated with diet, smoking, and general and central adiposity. Am J Clin Nutr 73, 777–785.
363Winklhofer-Roob, BM, Sargsyan, K & Maritschnegg, M (2005) Relations between antioxidants and biomarkers of consumption of fruits and vegetables and body mass index in the STYrian Juvenile Obesity Study (STYJOBS). Int J Obes 29, S150.
364Manach, C, Scalbert, A, Morand, C, et al. (2004) Polyphenols: food sources and bioavailability. Am J Clin Nutr 79, 727–747.
365Kuhnau, J (1976) The flavonoids. A class of semi-essential food components: their role in human nutrition. World Rev Nutr Diet 24, 117–191.
366Baumann, J, von Bruchhausen, F & Wurm, G (1980) Flavonoids and related compounds as inhibition of arachidonic acid peroxidation. Prostaglandins 20, 627–639.
367Lee, TP, Matteliano, ML & Middleton, E Jr (1982) Effect of quercetin on human polymorphonuclear leukocyte lysosomal enzyme release and phospholipid metabolism. Life Sci 31, 2765–2774.
368Welton, AF, Tobias, LD, Fiedler-Nagy, C, et al. (1986) Effect of flavonoids on arachidonic acid metabolism. Prog Clin Biol Res 213, 231–242.
369Noreen, Y, Serrano, G, Perera, P, et al. (1998) Flavan-3-ols isolated from some medicinal plants inhibiting COX-1 and COX-2 catalysed prostaglandin biosynthesis. Planta Med 64, 520–524.
370Chiesi, M & Schwaller, R (1995) Inhibition of constitutive endothelial NO-synthase activity by tannin and quercetin. Biochem Pharmacol 49, 495–501.
371Kim, OK, Murakami, A, Nakamura, Y, et al. (1998) Screening of edible Japanese plants for nitric oxide generation inhibitory activities in RAW 264.7 cells. Cancer Lett 125, 199–207.
372Liang, YC, Huang, YT, Tsai, SH, et al. (1999) Suppression of inducible cyclooxygenase and inducible nitric oxide synthase by apigenin and related flavonoids in mouse macrophages. Carcinogenesis 20, 1945–1952.
373Kim, HK, Cheon, BS, Kim, YH, et al. (1999) Effects of naturally occurring flavonoids on nitric oxide production in the macrophage cell line RAW 264.7 and their structure-activity relationships. Biochem Pharmacol 58, 759–765.
374Geng, Y, Zhang, B & Lotz, M (1993) Protein tyrosine kinase activation is required for lipopolysaccharide induction of cytokines in human blood monocytes. J Immunol 151, 6692–6700.
375Cho, JY, Kim, PS, Park, J, et al. (2000) Inhibitor of tumor necrosis factor-alpha production in lipopolysaccharide-stimulated RAW264.7 cells from Amorpha fruticosa. J Ethnopharmacol 70, 127–133.
376Wadsworth, TL, McDonald, TL & Koop, DR (2001) Effects of Ginkgo biloba extract (EGb 761) and quercetin on lipopolysaccharide-induced signaling pathways involved in the release of tumor necrosis factor-alpha. Biochem Pharmacol 62, 963–974.
377Wadsworth, TL & Koop, DR (2003) Effects of Ginkgo biloba extract (EGb 761) and quercetin on lipopolysaccharide-induced release of nitric oxide. Chem Biol Interact 137, 43–58.
378Cho, SY, Park, SJ, Kwon, MJ, et al. (2003) Quercetin suppresses proinflammatory cytokines production through MAP kinases and NF-kappaB pathway in lipopolysaccharide-stimulated macrophage. Mol Cell Biochem 243, 153–160.
379Morikawa, K, Nonaka, M, Narahara, M, et al. (2003) Inhibitory effect of quercetin on carrageenan-induced inflammation in rats. Life Sci 74, 709–721.
380Takahashi, K, Morikawa, A, Kato, Y, et al. (2001) Flavonoids protect mice from two types of lethal shock induced by endotoxin. FEMS Immunol Med Microbiol 31, 29–33.
381Ueda, H, Yamazaki, C & Yamazaki, M (2004) A hydroxyl group of flavonoids affects oral anti-inflammatory activity and inhibition of systemic tumor necrosis factor-alpha production. Biosci Biotechnol Biochem 68, 119–125.
382Estruch, R, Sacanella, E, Badia, E, et al. (2004) Different effects of red wine and gin consumption on inflammatory biomarkers of atherosclerosis: a prospective randomized crossover trial. Effects of wine on inflammatory markers. Atherosclerosis 175, 117–123.
383Zern, TL, Wood, RJ, Greene, C, et al. (2005) Grape polyphenols exert a cardioprotective effect in pre- and postmenopausal women by lowering plasma lipids and reducing oxidative stress. J Nutr 135, 1911–1917.
384Widlansky, ME, Duffy, SJ, Hamburg, NM, et al. (2005) Effects of black tea consumption on plasma catechins and markers of oxidative stress and inflammation in patients with coronary artery disease. Free Radic Biol Med 38, 499–506.
385Song, Y, Manson, JE, Buring, JE, et al. (2005) Associations of dietary flavonoids with risk of type 2 diabetes, and markers of insulin resistance and systemic inflammation in women: a prospective study and cross-sectional analysis. J Am Coll Nutr 24, 376–384.
386Bogani, P, Galli, C, Villa, M, et al. (2007) Postprandial anti-inflammatory and antioxidant effects of extra virgin olive oil. Atherosclerosis 190, 181–186.
387Rolfe, R (1996) . In Gastrointentestinal Microbiology, , [Mackie, RI, White, BA and Isaacson, RE, editors]. New York: Chapman & Hall.
388Holzapfel, WH (2006) . In Probiotics in Food Safety and Human Health, pp. 1–33 [Goktepe, I, Juneja, VK and Ahmedna, M, editors]. Boca Raton, FL: CRC Press.
389Edwards, CA & Parrett, AM (2002) Intestinal flora during the first months of life: new perspectives. Br J Nutr 88, Suppl. 1, S11–S18.
390Holzapfel, WH, Haberer, P, Snel, J, et al. (1998) Overview of gut flora and probiotics. Int J Food Microbiol 41, 85–101.
391Rhee, KJ, Sethupathi, P, Driks, A, et al. (2004) Role of commensal bacteria in development of gut-associated lymphoid tissues and preimmune antibody repertoire. J Immunol 172, 1118–1124.
392Tanaka, K & Ishikawa, H (2004) Role of intestinal bacterial flora in oral tolerance induction. Histol Histopathol 19, 907–914.
393Yamanaka, T, Helgeland, L, Farstad, IN, et al. (2003) Microbial colonization drives lymphocyte accumulation and differentiation in the follicle-associated epithelium of Peyer's patches. J Immunol 170, 816–822.
394Wostmann, BS (1996) Germfree and Gnotobiotic Animal Models. Boca Raton, FL: CRC Press.
395Ouwehand, A, Isolauri, E & Salminen, S (2002) The role of the intestinal microflora for the development of the immune system in early childhood. Eur J Nutr 41, Suppl. 1, I32–I37.
396Kalliomaki, M, Kirjavainen, P, Eerola, E, et al. (2001) Distinct patterns of neonatal gut microflora in infants in whom atopy was and was not developing. J Allergy Clin Immunol 107, 129–134.
397Rautava, S, Ruuskanen, O, Ouwehand, A, et al. (2004) The hygiene hypothesis of atopic disease–an extended version. J Pediatr Gastroenterol Nutr 38, 378–388.
398Sudo, N, Sawamura, S, Tanaka, K, et al. (1997) The requirement of intestinal bacterial flora for the development of an IgE production system fully susceptible to oral tolerance induction. J Immunol 159, 1739–1745.
399Macfarlane, S & Macfarlane, GT (2003) . In Gut Flora, Nutrition, Immunity and Health, [Fuller, R and Perdigon, G, editors]. Oxford: Blackwell Publishing.
400Gibson, GR & Roberfroid, MB (1995) Dietary modulation of the human colonic microbiota: introducing the concept of prebiotics. J Nutr 125, 1401–1412.
401Fuller, R & Gibson, GR (1997) Modification of the intestinal microflora using probiotics and prebiotics. Scand J Gastroenterol Suppl 222, 28–31.
402Fooks, LJ, Fuller, R & Gibson, GR (1999) Prebiotics, probiotics and human gut microbiology. Int Dairy J 9, 53–61.
403van Loo, J (2006) . In Prebiotics: Development & Application, pp. 57–100 [Gibson, GR and Rastall, RA, editors]. Chichester: John Wiley & Sons.
404van Loo, J, Coussement, P, de Leenheer, L, et al. (1995) On the presence of inulin and oligofructose as natural ingredients in the western diet. Crit Rev Food Sci Nutr 35, 525–552.
405Rastall, RA (2006) . In Prebiotics: Development & Application, pp. 101–110 [Gibson, GR and Rastall, RA, editors]. Chichester: John Wiley & Sons.
406Videla, S, Vilaseca, J, Antolin, M, et al. (2001) Dietary inulin improves distal colitis induced by dextran sodium sulfate in the rat. Am J Gastroenterol 96, 1486–1493.
407Schultz, M, Munro, K, Tannock, GW, et al. (2004) Effects of feeding a probiotic preparation (SIM) containing inulin on the severity of colitis and on the composition of the intestinal microflora in HLA-B27 transgenic rats. Clin Diagn Lab Immunol 11, 581–587.
408Hoentjen, F, Welling, GW, Harmsen, HJ, et al. (2005) Reduction of colitis by prebiotics in HLA-B27 transgenic rats is associated with microflora changes and immunomodulation. Inflamm Bowel Dis 11, 977–985.
409Femia, AP, Luceri, C, Dolara, P, et al. (2002) Antitumorigenic activity of the prebiotic inulin enriched with oligofructose in combination with the probiotics Lactobacillus rhamnosus and Bifidobacterium lactis on azoxymethane-induced colon carcinogenesis in rats. Carcinogenesis 23, 1953–1960.
410Saavedra, JM, Tschernia, A, Moore, N, et al. (1999) Gastro-intestinal function in infants consuming a weaning food supplemented with oligo-fructose, a prebiotic. J Pediatr Gastroenterol Nutr 29, A95.
411Waligora-Dupriet, AJ, Campeotto, F, Nicolis, I, et al. (2007) Effect of oligofructose supplementation on gut microflora and well-being in young children attending a day care centre. Int J Food Microbiol 113, 108–113.
412Moro, G, Arslanoglu, S, Stahl, B, et al. (2006) A mixture of prebiotic oligosaccharides reduces the incidence of atopic dermatitis during the first six months of age. Arch Dis Child 91, 814–819.
413Welters, CF, Heineman, E, Thunnissen, FB, et al. (2002) Effect of dietary inulin supplementation on inflammation of pouch mucosa in patients with an ileal pouch-anal anastomosis. Dis Colon Rectum 45, 621–627.
414Casellas, F, Borruel, N, Torrejon, A, et al. (2007) Oral oligofructose-enriched inulin supplementation in acute ulcerative colitis is well tolerated and associated with lowered faecal calprotectin. Aliment Pharmacol Ther 25, 1061–1067.
415FAO-WHO (2001) .
416Bergonzelli, GE, Granato, D, Pridmore, RD, et al. (2006) GroEL of Lactobacillus johnsonii La1 (NCC 533) is cell surface associated: potential role in interactions with the host and the gastric pathogen Helicobacter pylori. Infect Immun 74, 425–434.
417Buck, BL, Altermann, E, Svingerud, T, et al. (2005) Functional analysis of putative adhesion factors in Lactobacillus acidophilus NCFM. Appl Environ Microbiol 71, 8344–8351.
418Penner, R, Fedorak, RN & Madsen, KL (2005) Probiotics and nutraceuticals: non-medicinal treatments of gastrointestinal diseases. Curr Opin Pharmacol 5, 596–603.
419Petrof, EO, Kojima, K, Ropeleski, MJ, et al. (2004) Probiotics inhibit nuclear factor-kappaB and induce heat shock proteins in colonic epithelial cells through proteasome inhibition. Gastroenterology 127, 1474–1487.
420Cario, E, Gerken, G & Podolsky, DK (2004) Toll-like receptor 2 enhances ZO-1-associated intestinal epithelial barrier integrity via protein kinase C. Gastroenterology 127, 224–238.
421Neish, AS, Gewirtz, AT, Zeng, H, et al. (2000) Prokaryotic regulation of epithelial responses by inhibition of IkappaB-alpha ubiquitination. Science 289, 1560–1563.
422Kelly, D, Campbell, JI, King, TP, et al. (2004) Commensal anaerobic gut bacteria attenuate inflammation by regulating nuclear-cytoplasmic shuttling of PPAR-gamma and RelA. Nat Immunol 5, 104–112.
423O'Hara, AM, O'Regan, P, Fanning, A, et al. (2006) Functional modulation of human intestinal epithelial cell responses by Bifidobacterium infantis and Lactobacillus salivarius. Immunology 118, 202–215.
424Ruiz, PA, Hoffmann, M, Szcesny, S, et al. (2005) Innate mechanisms for Bifidobacterium lactis to activate transient pro-inflammatory host responses in intestinal epithelial cells after the colonization of germ-free rats. Immunology 115, 441–450.
425Miettinen, M, Lehtonen, A, Julkunen, I, et al. (2000) Lactobacilli and streptococci activate NF-kappa B and STAT signaling pathways in human macrophages. J Immunol 164, 3733–3740.
426Matsuguchi, T, Takagi, A, Matsuzaki, T, et al. (2003) Lipoteichoic acids from Lactobacillus strains elicit strong tumor necrosis factor alpha-inducing activities in macrophages through Toll-like receptor 2. Clin Diagn Lab Immunol 10, 259–266.
427Smits, HH, Engering, A, van der Kleij, D, et al. (2005) Selective probiotic bacteria induce IL-10-producing regulatory T cells in vitro by modulating dendritic cell function through dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin. J Allergy Clin Immunol 115, 1260–1267.
428Hahm, KB, Im, YH, Lee, C, et al. (2000) Loss of TGF-beta signaling contributes to autoimmune pancreatitis. J Clin Invest 105, 1057–1065.
429Monteleone, G, Kumberova, A, Croft, NM, et al. (2001) Blocking Smad7 restores TGF-beta1 signaling in chronic inflammatory bowel disease. J Clin Invest 108, 601–609.
430Di Giocinto, C, Marinaro, M, Sanchez, M, et al. (2005) Probiotics ameliorate recurrent Th1-mediated murine colitis by inducing IL-10 and IL-10-dependent TGF-beta-bearing regulatory cells. J Immunol 174, 3237–3246.
431Fujii, T, Ohtsuka, Y, Lee, T, et al. (2006) Bifidobacterium breve enhances transforming growth factor beta1 signaling by regulating Smad7 expression in preterm infants. J Pediatr Gastroenterol Nutr 43, 83–88.
432Mimura, T, Rizzello, F, Helwig, U, et al. (2004) Once daily high dose probiotic therapy (VSL#3) for maintaining remission in recurrent or refractory pouchitis. Gut 53, 108–114.
433Kuisma, J, Mentula, S, Jarvinen, H, et al. (2003) Effect of Lactobacillus rhamnosus GG on ileal pouch inflammation and microbial flora. Aliment Pharmacol Ther 17, 509–515.
434Gupta, P, Andrew, H, Kirschner, BS, et al. (2000) Is Lactobacillus GG helpful in children with Crohn's disease? Results of a preliminary, open-label study. J Pediatr Gastroenterol Nutr 31, 453–457.
435Schultz, M, Timmer, A, Herfarth, HH, et al. (2004) Lactobacillus GG in inducing and maintaining remission of Crohn's disease. BMC Gastroenterol 4, 5.
436Prantera, C, Scribano, ML, Falasco, G, et al. (2002) Ineffectiveness of probiotics in preventing recurrence after curative resection for Crohn's disease: a randomised controlled trial with Lactobacillus GG. Gut 51, 405–409.
437Marteau, P, Lemann, M, Seksik, P, et al. (2006) Ineffectiveness of Lactobacillus johnsonii LA1 for prophylaxis of postoperative recurrence in Crohn's disease: a randomised, double blind, placebo controlled GETAID trial. Gut 55, 842–847.
438Van Gossum, A, Dewit, O, Louis, E, et al. (2007) Multicenter randomized-controlled clinical trial of probiotics (Lactobacillus johnsonii, LA1) on early endoscopic recurrence of Crohn's disease after lleo-caecal resection. Inflamm Bowel Dis 13, 135–142.
439Kruis, W, Fric, P, Pokrotnieks, J, et al. (2004) Maintaining remission of ulcerative colitis with the probiotic Escherichia coli Nissle 1917 is as effective as with standard mesalazine. Gut 53, 1617–1623.
440Rembacken, BJ, Snelling, AM, Hawkey, PM, et al. (1999) Non-pathogenic Escherichia coli versus mesalazine for the treatment of ulcerative colitis: a randomised trial. Lancet 354, 635–639.
441Tursi, A, Brandimarte, G, Giorgetti, GM, et al. (2004) Low-dose balsalazide plus a high-potency probiotic preparation is more effective than balsalazide alone or mesalazine in the treatment of acute mild-to-moderate ulcerative colitis. Med Sci Monit 10, I126–I131.
442Zocco, MA, dal Verme, LZ, Cremonini, F, et al. (2006) Efficacy of Lactobacillus GG in maintaining remission of ulcerative colitis. Aliment Pharmacol Ther 23, 1567–1574.
443Cui, HH, Chen, CL, Wang, JD, et al. (2004) Effects of probiotic on intestinal mucosa of patients with ulcerative colitis. World J Gastroenterol 10, 1521–1525.
444Ishikawa, H, Akedo, I, Umesaki, Y, et al. (2003) Randomized controlled trial of the effect of bifidobacteria-fermented milk on ulcerative colitis. J Am Coll Nutr 22, 56–63.
445Rovensky, J, Svik, K, Stancikova, M, et al. (2002) Treatment of experimental adjuvant arthritis with the combination of methotrexate and lyophilized Enterococcus faecium enriched with organic selenium. Folia Microbiol (Praha) 47, 573–578.
446Hatakka, K, Martio, J, Korpela, M, et al. (2003) Effects of probiotic therapy on the activity and activation of mild rheumatoid arthritis – a pilot study. Scand J Rheumatol 32, 211–215.
447Shida, K, Makino, K, Morishita, A, et al. (1998) Lactobacillus casei inhibits antigen-induced IgE secretion through regulation of cytokine production in murine splenocyte cultures. Int Arch Allergy Immunol 115, 278–287.
448Matsuzaki, T, Yamazaki, R, Hashimoto, S, et al. (1998) The effect of oral feeding of Lactobacillus casei strain Shirota on immunoglobulin E production in mice. J Dairy Sci 81, 48–53.
449Murosaki, S, Yamamoto, Y, Ito, K, et al. (1998) Heat-killed Lactobacillus plantarum L-137 suppresses naturally fed antigen-specific IgE production by stimulation of IL-12 production in mice. J Allergy Clin Immunol 102, 57–64.
450Shida, K, Takahashi, R, Iwadate, E, et al. (2002) Lactobacillus casei strain Shirota suppresses serum immunoglobulin E and immunoglobulin G1 responses and systemic anaphylaxis in a food allergy model. Clin Exp Allergy 32, 563–570.
451Björkstén, B, Sepp, E, Julge, K, et al. (2001) Allergy development and the intestinal microflora during the first year of life. J Allergy Clin Immunol 108, 516–520.
452Ouwehand, AC, Isolauri, E,