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Monitoring immune modulation by nutrition in the general population: identifying and substantiating effects on human health

  • Ruud Albers (a1), Raphaëlle Bourdet-Sicard (a2), Deborah Braun (a3), Philip C. Calder (a4), Udo Herz (a5), Claude Lambert (a6), Irene Lenoir-Wijnkoop (a7), Agnès Méheust (a8), Arthur Ouwehand (a9), Phoukham Phothirath (a10), Tomoyuki Sako (a11), Seppo Salminen (a12), André Siemensma (a13), Henk van Loveren (a14) and Ulrich Sack (a15)...


Optimal functioning of the immune system is crucial to human health, and nutrition is one of the major exogenous factors modulating different aspects of immune function. Currently, no single marker is available to predict the effect of a dietary intervention on different aspects of immune function. To provide further guidance on the assessment and interpretation of the modulation of immune functions due to nutrition in the general population, International Life Sciences Institute Europe commissioned a group of experts from academia, government and the food industry to prepare a guidance document. A draft of this paper was refined at a workshop involving additional experts. First, the expert group defined criteria to evaluate the usefulness of immune function markers. Over seventy-five markers were scored within the context of three distinct immune system functions: defence against pathogens; avoidance or mitigation of allergy; control of low-grade (metabolic) inflammation. The most useful markers were subsequently classified depending on whether they by themselves signify clinical relevance and/or involvement of immune function. Next, five theoretical scenarios were drafted describing potential changes in the values of markers compared with a relevant reference range. Finally, all elements were combined, providing a framework to aid the design and interpretation of studies assessing the effects of nutrition on immune function. This stepwise approach offers a clear rationale for selecting markers for future trials and provides a framework for the interpretation of outcomes. A similar stepwise approach may also be useful to rationalise the selection and interpretation of markers for other physiological processes critical to the maintenance of health and well-being.

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The online version of this paper is published within an Open Access environment subject to the conditions of the Creative Attribution-NonCommercial-ShareAlike licence

Corresponding author

Correspondence: ILSI Europe a.i.s.b.l. - Avenue E. Mounier 83, Box 6 - 1200 Brussels - Belgium Email: - Fax: +32 2 762 00 44


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1Albers, R, Antoine, JM, Bourdet-Sicard, R, et al. (2005) Markers to measure immunomodulation in human nutrition intervention studies. Br J Nutr 94, 452481.
2Calder, PC, Albers, R, Antoine, JM, et al. (2009) Inflammatory disease processes and interactions with nutrition. Br J Nutr 101, Suppl. 1, S1S45.
3Corthesy, B, Gaskins, HR & Mercenier, A (2007) Cross-talk between probiotic bacteria and the host immune system. J Nutr 137, 781S790S.
4Esfahani, A, Wong, JMW, Truan, J, et al. (2011) Health effects of mixed fruit and vegetable concentrates: a systematic review of the clinical interventions. J Am Coll Nutr 30, 285294.
5Florentino, RF (2009) Symposium on diet, nutrition and immunity. Asia Pac J Clin Nutr 18, 137142.
6Forsythe, P & Bienenstock, J (2010) Immunomodulation by commensal and probiotic bacteria. Immunol Invest 39, 429448.
7Gourbeyre, P, Denery, S & Bodinier, M (2011) Probiotics, prebiotics, and synbiotics: impact on the gut immune system and allergic reactions. J Leukoc Biol 89, 685695.
8Leavy, O (2011) Mucosal immunology: the ‘AHR diet’ for mucosal homeostasis. Nat Rev Immunol 11, 806.
9Lenoir-Wijnkoop, I, Sanders, ME, Cabana, MD, et al. (2007) Probiotic and prebiotic influence beyond the intestinal tract. Nutr Rev 65, 469489.
10Lomax, AR & Calder, PC (2009) Probiotics, immune function, infection and inflammation: a review of the evidence from studies conducted in humans. Curr Pharm Design 15, 14281518.
11Lomax, AR & Calder, PC (2009) Prebiotics, immune function, infection and inflammation: a review of the evidence. Br J Nutr 101, 633658.
12Monk, JM, Hou, TY & Chapkin, RS (2011) Recent advances in the field of nutritional immunology. Expert Rev Clin Immunol 7, 747749.
13Rowland, I, Capurso, L, Collins, K, et al. (2010) Current level of consensus on probiotic science – report of an expert meeting – London, 23 November 2009. Gut Microbes 1, 436439.
14Valdés-Ramos, R, Martinez-Carrillo, BE, Aranda-Gonzalez, II, et al. (2010) Diet exercise and gut mucosal immunity. Proc Nutr Soc 69, 644650.
15van't Land, B, Schijf, MA, Martin, R, et al. (2011) Influencing mucosal homeostasis and immune responsiveness: the impact of nutrition and pharmaceuticals. Eur J Pharmacol 668, Suppl. 1, S101S107.
16Veldhoen, M & Brucklacher-Waldert, V (2012) Dietary influences on intestinal immunity. Nat Rev Immunol 12, 696708.
17Wallace, TC, Guarner, F, Madsen, K, et al. (2011) Human gut microbiota and its relationship to health and disease. Nutr Rev 69, 392403.
18Walsh, NP, Gleeson, M, Shephard, RJ, et al. (2011) Position statement. Part one: immune function and exercise. Exerc Immunol Rev 17, 663.
19Walsh, NP, Gleeson, M, Pyne, DB, et al. (2011) Position statement. Part two: maintaining immune health. Exerc Immunol Rev 17, 64103.
20Wichers, H (2009) Immunomodulation by food: promising concept for mitigating allergic disease? Anal Bioanal Chem 395, 3745.
21Yan, F & Polk, DB (2011) Probiotics and immune health. Curr Opin Gastroenterol 27, 496501.
22Afacan, NJ, Fjell, CD & Hancock, REW (2012) A systems biology approach to nutritional immunology – focus on innate immunity. Mol Aspects Med 33, 1425.
23Calder, PC & Kew, S (2002) The immune system: a target for functional foods? Br J Nutr 88, Suppl. 2, S165S177.
24Calder, PC (2007) Immunological parameters: what do they mean? J Nutr 137, 773S780S.
25Cummings, JH, Antoine, JM, Azpiroz, F, et al. (2004) PASSCLAIM – gut health and immunity. Eur J Nutr 43, Suppl. 2, II118II173.
26Duramad, P & Holland, NT (2011) Biomarkers of immunotoxicity for environmental and public health research. Int J Environ Res Public Health 8, 13881401.
27Haller, D, Antoine, JM, Bengmark, S, et al. (2010) Guidance for substantiating the evidence for beneficial effects of probiotics: probiotics in chronic inflammatory bowel disease and the functional disorder irritable bowel syndrome. J Nutr 140, 690S697S.
28Maecker, HT, McCoy, JP Jr, Amos, M, et al. (2010) A model for harmonizing flow cytometry in clinical trials. Nat Immunol 11, 975978.
29EFSA Panel on Dietetic Products Nutrition and Allergies (NDA) (2011) Guidance on the scientific requirements for health claims related to gut and immune function. EFSA J 9, 1984.
30Hamer, M, Wolvers, D & Albers, R (2004) Using stress models to evaluate immuno-modulating effects of nutritional intervention in healthy individuals. J Am Coll Nutr 23, 637646.
31Calder, PC, Ahluwalia, N, Albers, R, et al. (2012) A consideration of biomarkers to be used for evaluation of inflammation in human nutritional studies. Br J Nutr 109, Suppl. 1, S1S34.
32Calder, PC, Ahluwalia, N, Brouns, F, et al. (2011) Dietary factors and low-grade inflammation in relation to overweight and obesity. Br J Nutr 106, Suppl. 3, S5S78.
33vel Szic, KS, Ndlovu, MN, Haegeman, G, et al. (2010) Nature or nurture: let food be your epigenetic medicine in chronic inflammatory disorders. Biochem Pharmacol 80, 18161832.
34Gouin, JP, Hantsoo, L & Kiecolt-Glaser, JK (2008) Immune dysregulation and chronic stress among older adults: a review. Neuroimmunomodulation 15, 251259.
35Duramad, P, Tager, IB & Holland, NT (2007) Cytokines and other immunological biomarkers in children's environmental health studies. Toxicol Lett 172, 4859.
36Pae, M, Meydani, SN & Wu, D (2012) The role of nutrition in enhancing immunity in aging. Aging Dis 3, 91129.
37Darnall, BD & Suarez, EC (2009) Sex and gender in psychoneuroimmunology research: past, present and future. Brain Behav Immun 23, 595604.
38Habbal, OA & Al-Jabri, AA (2009) Circadian rhythm and the immune response: a review. Int Rev Immunol 28, 93108.
39Bollinger, T, Bollinger, A, Oster, H, et al. (2010) Sleep, immunity, and circadian clocks: a mechanistic model. Gerontology 56, 574580.
40Cunniffe, B, Griffiths, H, Proctor, W, et al. (2011) Mucosal immunity and illness incidence in elite rugby union players across a season. Med Sci Sports Exerc 43, 388397.
41Barriga-Ibars, C, Rodriguez-Moratinos, AB, Esteban, S, et al. (2005) [Interrelations between sleep and the immune status]. Rev Neurol 40, 548556.
42Brubaker, AL, Palmer, JL & Kovacs, EJ (2011) Age-related Dysregulation of Inflammation and Innate Immunity: Lessons Learned from Rodent Models. Aging Dis 2, 346360.
43Lau, S, Gerhold, K, Zimmermann, K, et al. (2012) Oral application of bacterial lysate in infancy decreases the risk of atopic dermatitis in children with 1 atopic parent in a randomized, placebo-controlled trial. J Allergy Clin Immunol 129, 10401047.
44Hojsak, I, Snovak, N, Abdovic, S, et al. (2010) Lactobacillus GG in the prevention of gastrointestinal and respiratory tract infections in children who attend day care centers: a randomized, double-blind, placebo-controlled trial. Clin Nutr 29, 312316.
45Guillemard, E, Tanguy, J, Flavigny, A, et al. (2010) Effects of consumption of a fermented dairy product containing the probiotic Lactobacillus casei DN-114 001 on common respiratory and gastrointestinal infections in shift workers in a randomized controlled trial. J Am Coll Nutr 29, 455468.
46Hoveyda, N, Heneghan, C, Mahtani, KR, et al. (2009) A systematic review and meta-analysis: probiotics in the treatment of irritable bowel syndrome. BMC Gastroenterol 9, 15.
47Sherman, PM, Cabana, M, Gibson, GR, et al. (2009) Potential roles and clinical utility of prebiotics in newborns, infants, and children: proceedings from a global prebiotic summit meeting, New York City, June 27–28, 2008. J Pediatr 155, S61S70.
48Usai-Satta, P, Scarpa, M, Oppia, F, et al. (2012) Lactose malabsorption and intolerance: what should be the best clinical management? World J Gastrointest Pharmacol Ther 3, 2933.
49van Meijl, LE & Mensink, RP (2010) Effects of low-fat dairy consumption on markers of low-grade systemic inflammation and endothelial function in overweight and obese subjects: an intervention study. Br J Nutr 104, 15231527.
50Graat, JM, Schouten, EG & Kok, FJ (2002) Effect of daily vitamin E and multivitamin-mineral supplementation on acute respiratory tract infections in elderly persons: a randomized controlled trial. JAMA 288, 715721.
51Ezzelle, J, Rodriguez-Chavez, IR, Darden, JM, et al. (2008) Guidelines on good clinical laboratory practice: bridging operations between research and clinical research laboratories. J Pharm Biomed Anal 46, 1829.
52Francisco, G, Hernandez, C & Simo, R (2006) Serum markers of vascular inflammation in dyslipemia. Clin Chim Acta 369, 116.
53 National Institute of Allergy and Infectious Diseases (2009) Requirements for DAIDS Funded and/or Sponsored Laboratories in Clinical Trials.
54Stevens, W (2003) Good clinical laboratory practice (GCLP): the need for a hybrid of good laboratory practice and good clinical practice guidelines/standards for medical testing laboratories conducting clinical trials in developing countries. Qual Assur 10, 8389.
55Stiles, T & Grant, V (2011) Good Clinical Laboratory Practice (GCLP). Ipswich: BARQA.
56Macey, MG, McCarthy, DA, Davies, C, et al. (1997) The Q-Prep system: effects on the apparent expression of leucocyte cell surface antigens. Cytometry 30, 6771.
57Prabhakar, U, Eirikis, E, Reddy, M, et al. (2004) Validation and comparative analysis of a multiplexed assay for the simultaneous quantitative measurement of Th1/Th2 cytokines in human serum and human peripheral blood mononuclear cell culture supernatants. J Immunol Methods 291, 2738.
58Sack, U, Gerling, F & Tarnok, A (2007) Age-related lymphocyte subset changes in the peripheral blood of healthy children – a meta-study. Transfus Med Hemother 34, 176181.
59Shearer, WT, Rosenblatt, HM, Gelman, RS, et al. (2003) Pediatric AIDS Clinical Trials Group. Lymphocyte subsets in healthy children from birth through 18 years of age: the Pediatric AIDS Clinical Trials Group P1009 study. J Allergy Clin Immunol 112, 973980.
60Gwaltney, JM Jr & Hendley, JO (2001) Respiratory transmission. In Epidemiologic Methods for the Study of Infectious Diseases [Thomas, JC and Weber, DJ, editors]. New York, NY: Oxford University Press.
61Jackson, GG, Dowling, HF, Anderson, TO, et al. (1960) Susceptibility and immunity to common upper respiratory viral infections – the common cold. Ann Intern Med 53, 719738.
62Jackson, GG, Dowling, HF & Muldoon, RL (1962) Acute respiratory diseases of viral etiology. VII. Present concepts of the common cold. Am J Public Health Nations Health 52, 940945.
63Barrett, B, Brown, R, Mundt, M, et al. (2005) The Wisconsin Upper Respiratory Symptom Survey is responsive, reliable, and valid. J Clin Epidemiol 58, 609617.
64Barrett, B (2006) Relations among questionnaire and laboratory measures of rhinovirus infection. Eur Respir J 28, 358361.
65Barrett, B, Brown, RL, Mundt, MP, et al. (2009) Validation of a short form Wisconsin Upper Respiratory Symptom Survey (WURSS-21). Health Qual Life Outcomes 7, 76.
66Ruuska, T & Vesikari, T (1990) Rotavirus disease in Finnish children: use of numerical scores for clinical severity of diarrhoeal episodes. Scand J Infect Dis 22, 259267.
67World Health Organization (2005) The Treatment of Diarrhoea: A Manual for Physicians and Other Senior Health Workers. Geneva: WHO.
68Gelmetti, C & Colonna, C (2004) The value of SCORAD and beyond. Towards a standardized evaluation of severity? Allergy 59, Suppl. 78, 6165.
69Oranje, AP (2011) Practical issues on interpretation of scoring atopic dermatitis: SCORAD index, objective SCORAD, patient-oriented SCORAD and three-item severity score. Curr Probl Dermatol 41, 149155.
70Oranje, AP, Glazenburg, EJ, Wolkerstorfer, A, et al. (2007) Practical issues on interpretation of scoring atopic dermatitis: the SCORAD index, objective SCORAD and the three-item severity score. Br J Dermatol 157, 645648.
71Jauregui, I, Davila, I, Sastre, J, et al. (2011) Validation of ARIA (Allergic Rhinitis and its Impact on Asthma) classification in a pediatric population: the PEDRIAL study. Pediatr Allergy Immunol 22, 388392.
72Thomas, M, Kay, S, Pike, J, et al. (2009) The Asthma Control Test (ACT) as a predictor of GINA guideline-defined asthma control: analysis of a multinational cross-sectional survey. Prim Care Respir J 18, 4149.
73Zeiger, RS, Mellon, M, Chipps, B, et al. (2011) Test for Respiratory and Asthma Control in Kids (TRACK): clinically meaningful changes in score. J Allergy Clin Immunol 128, 983988.
74Bleda, MJ, Bolibar, I, Pares, R, et al. (2002) Reliability of the mini nutritional assessment (MNA) in institutionalized elderly people. J Nutr Health Aging 6, 134137.
75Wikby, K, Ek, AC & Christensson, L (2008) The two-step Mini Nutritional Assessment procedure in community resident homes. J Clin Nurs 17, 12111218.
76Turner, RB, Riker, DK & Gangemi, JD (2000) Ineffectiveness of echinacea for prevention of experimental rhinovirus colds. Antimicrob Agents Chemother 44, 17081709.
77Turner, RB & Cetnarowski, WE (2000) Effect of treatment with zinc gluconate or zinc acetate on experimental and natural colds. Clin Infect Dis 31, 12021208.
78Broadbent, DE, Broadbent, MH, Phillpotts, RJ, et al. (1984) Some further studies on the prediction of experimental colds in volunteers by psychological factors. J Psychosom Res 28, 511523.
79Tacket, CO, Binion, SB, Bostwick, E, et al. (1992) Efficacy of bovine milk immunoglobulin concentrate in preventing illness after Shigella flexneri challenge. Am J Trop Med Hyg 47, 276283.
80DeVincenzo, JP, Wilkinson, T, Vaishnaw, A, et al. (2010) Viral load drives disease in humans experimentally infected with respiratory syncytial virus. Am J Resp Crit Care Med 182, 13051314.
81Bovee-Oudenhoven, IMJ, Lettink-Wissink, MLG, van Doesburg, W, et al. (2003) Diarrhea caused by enterotoxigenic Escherichia coli infection of humans is inhibited by dietary calcium. Gastroenterology 125, 469476.
82Rolinck-Werninghaus, C, Niggemann, B, Grabenhenrich, L, et al. (2012) Outcome of oral food challenges in children in relation to symptom-eliciting allergen dose and allergen-specific IgE. Allergy 67, 951957.
83Zomer-Kooijker, K, Slieker, MG, Kentie, PA, et al. (2012) A prediction rule for food challenge outcome in children. Pediatr Allergy Immunol 23, 353359.
84Akerlund, A, Andersson, M, Leflein, J, et al. (2005) Clinical trial design, nasal allergen challenge models, and considerations of relevance to pediatrics, nasal polyposis, and different classes of medication. J Allergy Clin Immunol 115, S460S482.
85Rondon, C, Campo, P, Herrera, R, et al. (2011) Nasal allergen provocation test with multiple aeroallergens detects polysensitization in local allergic rhinitis. J Allergy Clin Immunol 128, 11921197.
86European Medicines Agency (EMEA) (2006) Guideline on Clinical Evaluation of New Vaccines. London: EMEA.
87Nauta, JJ, Beyer, WE & Osterhaus, AD (2009) On the relationship between mean antibody level, seroprotection and clinical protection from influenza. Biologicals 37, 216221.
88Committee for Proprietary Medicinal Products (1997) Note for Guidance on Harmonisation of Requirements for Influenza Vaccines. London: European Agency for the Evaluation of Medicinal Products.
89Ananworanich, J & Shearer, WT (2002) Delayed-type hypersensitivity skin testing. In Manual of Clinical Laboratory Immunology, pp. 212219 [Rose, NR, Hamilton, RG and Detrick, B, editors]. Washington, DC: ASM Press.
90Harper Smith, AD, Coakley, SL, Ward, MD, et al. (2011) Exercise-induced stress inhibits both the induction and elicitation phases of in vivo T-cell-mediated immune responses in humans. Brain Behav Immun 25, 11361142.
91Sleijffers, A, Garssen, J, de Gruijl, FR, et al. (2001) Influence of ultraviolet B exposure on immune responses following hepatitis B vaccination in human volunteers. J Invest Dermatol 117, 11441150.
92Ruutu, MP, Chen, X, Joshi, O, et al. (2011) Increasing mechanical stimulus induces migration of Langerhans cells and impairs the immune response to intracutaneously delivered antigen. Exp Dermatol 20, 534536.
93Marchiando, AM, Graham, WV & Turner, JR (2010) Epithelial barriers in homeostasis and disease. Annu Rev Pathol 5, 119144.
94Shimizu, M (2010) Interaction between food substances and the intestinal epithelium. Biosci Biotechnol Biochem 74, 232241.
95Turner, JR (2009) Intestinal mucosal barrier function in health and disease. Nat Rev Immunol 9, 799809.
96Wershil, BK & Furuta, GT (2008) 4. Gastrointestinal mucosal immunity. J Allergy Clin Immunol 121, S380S383.
97Darsow, U & Ring, J (2000) Airborne and dietary allergens in atopic eczema: a comprehensive review of diagnostic tests. Clin Exp Dermatol 25, 544551.
98Bousquet, J, Heinzerling, L, Bachert, C, et al. (2012) Practical guide to skin prick tests in allergy to aeroallergens. Allergy 67, 1824.
99Beyer, K & Teuber, SS (2005) Food allergy diagnostics: scientific and unproven procedures. Curr Opin Allergy Clin Immunol 5, 261266.
100Niggemann, B, Sielaff, B, Beyer, K, et al. (1999) Outcome of double-blind, placebo-controlled food challenge tests in 107 children with atopic dermatitis. Clin Exp Allergy 29, 9196.
101Gosepath, J, Amedee, RG & Mann, WJ (2005) Nasal provocation testing as an international standard for evaluation of allergic and nonallergic rhinitis. Laryngoscope 115, 512516.
102Litvyakova, LI & Baraniuk, JN (2001) Nasal provocation testing: a review. Ann Allergy Asthma Immunol 86, 355364.
103Fahlman, MM & Engels, HJ (2005) Mucosal IgA and URTI in American college football players: a year longitudinal study. Med Sci Sports Exerc 37, 374380.
104Gleeson, M, McDonald, WA, Pyne, DB, et al. (1999) Salivary IgA levels and infection risk in elite swimmers. Med Sci Sports Exerc 31, 6773.
105Gleeson, M (2000) Mucosal immune responses and risk of respiratory illness in elite athletes. Exerc Immunol Rev 6, 542.
106Isaacs, D, Webster, AD & Valman, HB (1984) Immunoglobulin levels and function in pre-school children with recurrent respiratory infections. Clin Exp Immunol 58, 335340.
107Lehtonen, OP, Tenovuo, J, Aaltonen, AS, et al. (1987) Immunoglobulins and innate factors of immunity in saliva of children prone to respiratory infections. Acta Pathol Microbiol Immunol Scand C 95, 3540.
108Mackinnon, LT (1999) Advances in Exercise and Immunology. Champaign, IL: Human Kinetics.
109Neville, V, Gleeson, M & Folland, JP (2008) Salivary IgA as a risk factor for upper respiratory infections in elite professional athletes. Med Sci Sports Exerc 40, 12281236.
110van Riet, E, Ainai, A, Suzuki, T, et al. (2012) Mucosal IgA responses in influenza virus infections; thoughts for vaccine design. Vaccine 30, 58935900.
111Kosnik, M, Silar, M, Bajrovic, N, et al. (2005) High sensitivity of basophils predicts side-effects in venom immunotherapy. Allergy 60, 14011406.
112Lambert, C, Guilloux, L, Dzviga, C, et al. (2003) Flow cytometry versus histamine release analysis of in vitro basophil degranulation in allergy to Hymenoptera venom. Cytometry B Clin Cytom 52, 1319.
113Rueff, F, Przybilla, B, Bilo, MB, et al. (2009) Predictors of severe systemic anaphylactic reactions in patients with Hymenoptera venom allergy: importance of baseline serum tryptase – a study of the European Academy of Allergology and Clinical Immunology Interest Group on Insect Venom Hypersensitivity. J Allergy Clin Immunol 124, 10471054.
114Holt, PG, Rowe, J, Kusel, M, et al. (2010) Toward improved prediction of risk for atopy and asthma among preschoolers: a prospective cohort study. J Allergy Clin Immunol 125, 653659, 659.e1–659.e7.
115Ott, H, Tenbrock, K, Baron, J, et al. (2011) Basophil activation test for the diagnosis of hymenoptera venom allergy in childhood: a pilot study. Klin Padiatr 223, 2732.
116Wensley, F, Gao, P, Burgess, S, et al. (2011) Association between C reactive protein and coronary heart disease: mendelian randomisation analysis based on individual participant data. BMJ 342, d548.
117Casas, JP, Shah, T, Hingorani, AD, et al. (2008) C-reactive protein and coronary heart disease: a critical review. J Intern Med 264, 295314.
118Strandberg, TE & Tilvis, RS (2000) C-reactive protein, cardiovascular risk factors, and mortality in a prospective study in the elderly. Arterioscler Thromb Vasc Biol 20, 10571060.
119Clapp, BR, Hirschfield, GM, Storry, C, et al. (2005) Inflammation and endothelial function: direct vascular effects of human C-reactive protein on nitric oxide bioavailability. Circulation 111, 15301536.
120Dowd, JB, Aiello, AE, Chyu, L, et al. (2011) Cytomegalovirus antibodies in dried blood spots: a minimally invasive method for assessing stress, immune function, and aging. Immun Ageing 8, 3.
121Guarino, A, Canani, RB, Spagnuolo, MI, et al. (1997) Oral bacterial therapy reduces the duration of symptoms and of viral excretion in children with mild diarrhea. J Pediatr Gastroenterol Nutr 25, 516.
122Guarner, F (2007) Studies with inulin-type fructans on intestinal infections, permeability, and inflammation. J Nutr 137, 2568S2571S.
123Lesourd, BM (1997) Nutrition and immunity in the elderly: modification of immune responses with nutritional treatments. Am J Clin Nutr 66, 478S484S.
124Mcfarland, LV & Elmer, GW (2006) Meta-analysis of probiotics for the prevention and treatment of acute pediatric diarrhea. Int J Prebiotics Probiotics 1, 6376.
125Meydani, SN (1993) Vitamin/mineral supplementation, the aging immune response, and risk of infection. Nutr Rev 51, 106109.
126Ngom, PT, Solon, J, Moore, SE, et al. (2011) Thymic function and T cell parameters in a natural human experimental model of seasonal infectious diseases and nutritional burden. J Biomed Sci 18, 41.
127Ongradi, J & Kovesdi, V (2010) Factors that may impact on immunosenescence: an appraisal. Immun Ageing 7, 7.
128Romeo, J, Nova, E, Warnberg, J, et al. (2010) Immunomodulatory effect of fibres, probiotics and synbiotics in different life-stages. Nutr Hosp 25, 341349.
129Sazawal, S, Hiremath, G, Dhingra, U, et al. (2006) Efficacy of probiotics in prevention of acute diarrhoea: a meta-analysis of masked, randomised, placebo-controlled trials. Lancet Infect Dis 6, 374382.
130Stowe, RP, Kozlova, EV, Yetman, DL, et al. (2007) Chronic herpes virus reactivation occurs in aging. Exp Gerontol 42, 563570.
131Szajewska, H, Skorka, A, Ruszczyäski, M, et al. (2007) Meta-analysis: Lactobacillus GG for treating acute diarrhoea in children. Aliment Pharmacol Ther 25, 871881.
132Vescovini, R, Biasini, C, Fagnoni, FF, et al. (2007) Massive load of functional effector CD4+ and CD8+ T cells against cytomegalovirus in very old subjects. J Immunol 179, 42834291.
133Peterson, KM, O'Shea, M, Stam, W, et al. (2009) Effects of dietary supplementation with conjugated linoleic acid on experimental human rhinovirus infection and illness. Antivir Ther 14, 3343.
134Porter, CK, Riddle, MS, Tribble, DR, et al. (2011) A systematic review of experimental infections with enterotoxigenic Escherichia coli (ETEC). Vaccine 29, 58695885.
135Turner, RB, Bauer, R, Woelkart, K, et al. (2005) An evaluation of Echinacea angustifolia in experimental rhinovirus infections. New Engl J Med 353, 341348.
136Hara, M, Tanaka, K & Hirota, Y (2005) Immune response to influenza vaccine in healthy adults and the elderly: association with nutritional status. Vaccine 23, 14571463.
137Wolvers, DA, van Herpen-Broekmans, WM, Logman, MH, et al. (2006) Effect of a mixture of micronutrients, but not of bovine colostrum concentrate, on immune function parameters in healthy volunteers: a randomized placebo-controlled study. Nutr J 5, 28.
138Gupta, K & Cooper, C (2008) A review of the role of CpG oligodeoxynucleotides as toll-like receptor 9 agonists in prophylactic and therapeutic vaccine development in infectious diseases. Drugs R D 9, 137145.
139Sangare, L, Manhart, L, Zehrung, D, et al. (2009) Intradermal hepatitis B vaccination: a systematic review and meta-analysis. Vaccine 27, 17771786.
140Gordon, DL, Sajkov, D, Woodman, RJ, et al. (2012) Randomized clinical trial of immunogenicity and safety of a recombinant H1N1/2009 pandemic influenza vaccine containing Advax polysaccharide adjuvant. Vaccine 30, 54075416.
141van Loveren, H, van Amsterdam, JG, Vandebriel, RJ, et al. (2001) Vaccine-induced antibody responses as parameters of the influence of endogenous and environmental factors. Environ Health Perspect 109, 757764.
142Dahlen, I, Lindberg, E, Janson, C, et al. (1999) Delayed type of hypersensitivity and late allergic reactions in patients with stable COPD. Chest 116, 16251631.
143Han, SN, Leka, LS, Lichtenstein, AH, et al. (2003) Effect of a therapeutic lifestyle change diet on immune functions of moderately hypercholesterolemic humans. J Lipid Res 44, 23042310.
144Hawkes, WC, Hwang, A & Alkan, Z (2009) The effect of selenium supplementation on DTH skin responses in healthy North American men. J Trace Elem Med Biol 23, 272280.
145Vukmanovic-Stejic, M, Reed, JR & Lacy, KE (2006) Mantoux Test as a model for a secondary immune response in humans. Immunol Lett 107, 93101.
146Wu, D, Han, SN, Meydani, M, et al. (2006) Effect of concomitant consumption of fish oil and vitamin E on T cell mediated function in the elderly: a randomized double-blind trial. J Am Coll Nutr 25, 300306.
147Nestle, FO, Di, MP, Qin, JZ, et al. (2009) Skin immune sentinels in health and disease. Nat Rev Immunol 9, 679691.
148Arvola, T, Moilanen, E & Vuento, R (2004) Weaning to hypoallergenic formula improves gut barrier function in breast-fed infants with atopic eczema. J Pediatr Gastroenterol Nutr 38, 9296.
149Gotteland, M, Andrews, M, Toledo, M, et al. (2008) Modulation of Helicobacter pylori colonization with cranberry juice and Lactobacillus johnsonii La1 in children. Nutrition 24, 421426.
150Westerbeek, EA, Hensgens, RL, Mihatsch, WA, et al. (2011) The effect of neutral and acidic oligosaccharides on stool viscosity, stool frequency and stool pH in preterm infants. Acta Paediatr 100, 14261431.
151Mullen, A, Gosset, L, Larke, N, et al. (2012) The effects of micronutrient-fortified complementary/replacement food on intestinal permeability and systemic markers of inflammation among maternally HIV-exposed and unexposed Zambian infants. Br J Nutr 107, 893902.
152Willumsen, JF, Darling, JC, Kitundu, JA, et al. (1997) Dietary management of acute diarrhoea in children: effect of fermented and amylase-digested weaning foods on intestinal permeability. J Pediatr Gastroenterol Nutr 24, 235.
153Cole, CR, Frem, JC, Schmotzer, B, et al. (2010) The rate of bloodstream infection is high in infants with short bowel syndrome: relationship with small bowel bacterial overgrowth, enteral feeding, and inflammatory and immune responses. J Pediatr 156, 941–7, 947.e1.
154de Oliveira, EP & Burini, RC (2011) Food-dependent, exercise-induced gastrointestinal distress. J Int Soc Sports Nutr 8, 12.
155Maes, M, Kubera, M, Leunis, JC, et al. (2012) Increased IgA and IgM responses against gut commensals in chronic depression: further evidence for increased bacterial translocation or leaky gut. J Affect Disord 141, 5562.
156Andreasen, AS, Larsen, N, Pedersen-Skovsgaard, T, et al. (2010) Effects of Lactobacillus acidophilus NCFM on insulin sensitivity and the systemic inflammatory response in human subjects. Br J Nutr 104, 18311838.
157Baldassarre, ME, Laforgia, N & Fanelli, M (2010) Lactobacillus GG improves recovery in infants with blood in the stools and presumptive allergic colitis compared with extensively hydrolyzed formula alone. J Pediatr 156, 397401.
158Ji, GE (2009) Probiotics in primary prevention of atopic dermatitis. Forum Nutr 61, 117128.
159Savilahti, E, Kukkonen, K & Kuitunen, M (2009) Probiotics in the treatment and prevention of allergy in children. World Allergy Organ J 2, 6976.
160Yoshimura, M, Enomoto, T, Dake, Y, et al. (2007) An evaluation of the clinical efficacy of tomato extract for perennial allergic rhinitis. Allergol Int 56, 225230.
161Mlynek, A, Zalewska-Janowska, A, Martus, P, et al. (2008) How to assess disease activity in patients with chronic urticaria? Allergy 63, 777780.
162Nermes, M, Kantele, JM, Atosuo, TJ, et al. (2011) Interaction of orally administered Lactobacillus rhamnosus GG with skin and gut microbiota and humoral immunity in infants with atopic dermatitis. Clin Exp Allergy 41, 370377.
163McBride, D, Keil, T, Grabenhenrich, L, et al. (2012) The EuroPrevall birth cohort study on food allergy: baseline characteristics of 12,000 newborns and their families from nine European countries. Pediatr Allergy Immunol 23, 230239.
164McLoughlin, RM & Mills, KHG (2011) Influence of gastrointestinal commensal bacteria on the immune responses that mediate allergy and asthma. J Allergy Clin Immunol 127, 10971107.
165Noverr, MC & Huffnagle, GB (2004) Does the microbiota regulate immune responses outside the gut? Trends Microbiol 12, 562568.
166Spergel, JM, Brown-Whitehorn, TF, Beausoleil, JL, et al. (2009) 14 years of eosinophilic esophagitis: clinical features and prognosis. J Pediatr Gastroenterol Nutr 48, 3036.
167Sucharew, H, Khoury, JC, Rao, M, et al. (2011) Predicting allergic disease at age four using an atopy predisposition score at age two: the application of item response theory. Pediatr Allergy Immunol 23, 195201.
168Canani, RB, Ruotolo, S, Auricchio, L, et al. (2007) Diagnostic accuracy of the atopy patch test in children with food allergy-related gastrointestinal symptoms. Allergy 62, 738743.
169Canani, RB, Buongiovanni, A, Nocerino, R, et al. (2011) Toward a standardized reading of the atopy patch test in children with suspected cow's milk allergy-related gastrointestinal symptoms. Allergy 66, 14991500.
170Martin, SF (2012) Contact dermatitis: from pathomechanisms to immunotoxicology. Exp Dermatol 21, 382389.
171Mehl, A, Rolinck-Werninghaus, C, Staden, U, et al. (2006) The atopy patch test in the diagnostic workup of suspected food-related symptoms in children. J Allergy Clin Immunol 118, 923929.
172Uter, W, Aberer, W, Armario-Hita, JC, et al. (2012) Current patch test results with the European baseline series and extensions to it from the ‘European Surveillance System on Contact Allergy’ network, 2007–2008. Contact Dermatitis 67, 919.
173Wassenberg, J, Nutten, S, Audran, R, et al. (2011) Effect of Lactobacillus paracasei ST11 on a nasal provocation test with grass pollen in allergic rhinitis. Clin Exp Allergy 41, 565573.
174Rondon, C, Campo, P, Togias, A, et al. (2012) Local allergic rhinitis: concept, pathophysiology, and management. J Allergy Clin Immunol 129, 14601467.
175Scadding, GW, Calderon, MA, Bellido, V, et al. (2012) Optimisation of grass pollen nasal allergen challenge for assessment of clinical and immunological outcomes. J Immunol Methods 384, 2532.
176Carty, CL, Heagerty, P & Nakayama, K (2006) Inflammatory response after influenza vaccination in men with and without carotid artery disease. Arterioscler Thromb Vasc Biol 26, 27382744.
177Derosa, G, Ferrari, I, D'Angelo, A, et al. (2009) Oral fat load effects on inflammation and endothelial stress markers in healthy subjects. Heart Vessels 24, 204210.
178Kop, WJ, Weissman, NJ, Zhu, J, et al. (2008) Effects of acute mental stress and exercise on inflammatory markers in patients with coronary artery disease and healthy controls. Am J Cardiol 101, 767773.
179Wopereis, S, Rubingh, CM, van Erk, MJ, et al. (2009) Metabolic profiling of the response to an oral glucose tolerance test detects subtle metabolic changes. PLoS One 4, e4525.
180Parks, CG, Andrew, ME, Blanciforti, LA, et al. (2007) Variation in the WBC differential count and other factors associated with reporting of herpes labialis: a population-based study of adults. FEMS Immunol Med Microbiol 51, 336343.
181Pfister, R, Sharp, SJ, Luben, R, et al. (2012) Differential white blood cell count and incident heart failure in men and women in the EPIC-Norfolk study. Eur Heart J 33, 523530.
182Wikby, A, Maxson, P, Olsson, J, et al. (1998) Changes in CD8 and CD4 lymphocyte subsets, T cell proliferation responses and non-survival in the very old: the Swedish longitudinal OCTO-immune study. Mech Ageing Dev 102, 187198.
183Wikby, A, Nilsson, BO, Forsey, R, et al. (2006) The immune risk phenotype is associated with IL-6 in the terminal decline stage: findings from the Swedish NONA immune longitudinal study of very late life functioning. Mech Ageing Dev 127, 695704.
184Minet-Quinard, R, Farges, MC, Thivat, E, et al. (2010) Neutrophils are immune cells preferentially targeted by retinoic acid in elderly subjects. Immun Ageing 7, 10.
185Varela, LM, Ortega, A, Bermudez, B, et al. (2011) A high-fat meal promotes lipid-load and apolipoprotein B-48 receptor transcriptional activity in circulating monocytes. Am J Clin Nutr 93, 918925.
186Walrand, S, Farges, MC, Dehaese, O, et al. (2005) In vivo and in vitro evidences that carotenoids could modulate the neutrophil respiratory burst during dietary manipulation. Eur J Nutr 44, 114120.
187Amulic, B, Cazalet, C, Hayes, GL, et al. (2012) Neutrophil function: from mechanisms to disease. Annu Rev Immunol 30, 459489.
188Filias, A, Theodorou, GL, Mouzopoulou, S, et al. (2011) Phagocytic ability of neutrophils and monocytes in neonates. BMC Pediatr 11, 29.
189Flannagan, RS, Jaumouille, V & Grinstein, S (2012) The cell biology of phagocytosis. Annu Rev Pathol 7, 6198.
190Shi, C & Pamer, EG (2011) Monocyte recruitment during infection and inflammation. Nat Rev Immunol 11, 762774.
191Strunk, T, Temming, P, Gembruch, U, et al. (2004) Differential maturation of the innate immune response in human fetuses. Pediatr Res 56, 219226.
192Hughes, DA, Wright, AJ, Finglas, PM, et al. (1997) The effect of beta-carotene supplementation on the immune function of blood monocytes from healthy male nonsmokers. J Lab Clin Med 129, 309317.
193Brtko, J, Rock, E, Nezbedova, P, et al. (2007) Age-related change in the retinoid X receptor beta gene expression in peripheral blood mononuclear cells of healthy volunteers: effect of 13-cis retinoic acid supplementation. Mech Ageing Dev 128, 594600.
194Santos, MS, Gaziano, JM, Leka, LS, et al. (1998) Beta-carotene-induced enhancement of natural killer cell activity in elderly men: an investigation of the role of cytokines. Am J Clin Nutr 68, 164170.
195Allegra, S, Deleine, C, Michael-Jubely, R, et al. (2006) Implementation of the EGFP-K562 flow cytometric NK test: determination of NK cytotoxic activity in healthy elderly volunteers before and after feeding. Cytometry A 69, 992998.
196Biron, CA, Nguyen, KB, Pien, GC, et al. (1999) Natural killer cells in antiviral defense: function and regulation by innate cytokines. Annu Rev Immunol 17, 189220.
197Hamerman, JA, Ogasawara, K & Lanier, LL (2005) NK cells in innate immunity. Curr Opin Immunol 17, 2935.
198Konjevic, G, Jurisic, V, Jovic, V, et al. (2012) Investigation of NK cell function and their modulation in different malignancies. Immunol Res 52, 139156.
199Lodoen, MB & Lanier, LL (2006) Natural killer cells as an initial defense against pathogens. Curr Opin Immunol 18, 391398.
200Murphy, WJ, Parham, P & Miller, JS (2012) NK cells – from bench to clinic. Biol Blood Marrow Transplant 18, S2S7.
201Sun, JC & Lanier, LL (2011) NK cell development, homeostasis and function: parallels with CD8(+) T cells. Nat Rev Immunol 11, 645657.
202Whiteside, TL (2001) Measurement of cytotoxic activity of NK/LAK cells. Curr Protoc Immunol Chapter 7, Unit 7.18.
203Ghanim, H, Sia, CL, Upadhyay, M, et al. (2010) Orange juice neutralizes the proinflammatory effect of a high-fat, high-carbohydrate meal and prevents endotoxin increase and Toll-like receptor expression. Am J Clin Nutr 91, 940949.
204Mena, MP, Sacanella, E, Vazquez-Agell, M, et al. (2009) Inhibition of circulating immune cell activation: a molecular antiinflammatory effect of the Mediterranean diet. Am J Clin Nutr 89, 248256.
205Trombetta, ES & Mellman, I (2005) Cell biology of antigen processing in vitro and in vivo. Annu Rev Immunol 23, 9751028.
206Rescigno, M (2010) Functional specialization of antigen presenting cells in the gastrointestinal tract. Curr Opin Immunol 22, 131136.
207Rescigno, M & Di, SA (2009) Dendritic cells in intestinal homeostasis and disease. J Clin Invest 119, 24412450.
208Rescigno, M & Chieppa, M (2005) Gut-level decisions in peace and war. Nat Med 11, 254255.
209Neefjes, J, Jongsma, ML, Paul, P, et al. (2011) Towards a systems understanding of MHC class I and MHC class II antigen presentation. Nat Rev Immunol 11, 823836.
210Guermonprez, P, Valladeau, J, Zitvogel, L, et al. (2002) Antigen presentation and T cell stimulation by dendritic cells. Annu Rev Immunol 20, 621667.
211Pascoe, MC, Crewther, SG, Carey, LM, et al. (2011) What you eat is what you are – a role for polyunsaturated fatty acids in neuroinflammation induced depression? Clin Nutr (Edinburgh Scotland) 30, 407415.
212Solis-Pereyra, B, Aattouri, N & Lemonnier, D (1997) Role of food in the stimulation of cytokine production. Am J Clin Nutr 66, 521S525S.
213Ouyang, W, Rutz, S, Crellin, NK, et al. (2011) Regulation and functions of the IL-10 family of cytokines in inflammation and disease. Annu Rev Immunol 29, 71109.
214Liu, Z, Yuan, X, Luo, Y, et al. (2009) Evaluating the effects of immunosuppressants on human immunity using cytokine profiles of whole blood. Cytokine 45, 141147.
215Gonzalez-Navajas, JM, Lee, J, David, M, et al. (2012) Immunomodulatory functions of type I interferons. Nat Rev Immunol 12, 125135.
216Viola, A & Luster, AD (2008) Chemokines and their receptors: drug targets in immunity and inflammation. Annu Rev Pharmacol Toxicol 48, 171197.
217Sallusto, F & Baggiolini, M (2008) Chemokines and leukocyte traffic. Nat Immunol 9, 949952.
218Sallusto, F & Mackay, CR (2004) Chemoattractants and their receptors in homeostasis and inflammation. Curr Opin Immunol 16, 724731.
219Hall, JA, Cannons, JL, Grainger, JR, et al. (2011) Essential role for retinoic acid in the promotion of CD4+ T cell effector responses via retinoic acid receptor alpha. Immunity 34, 435447.
220Hamer, DH, Sempertegui, F, Estrella, B, et al. (2009) Micronutrient deficiencies are associated with impaired immune response and higher burden of respiratory infections in elderly Ecuadorians. J Nutr 139, 113119.
221Hoyles, L & Vulevic, J (2008) Diet, immunity and functional foods. Adv Exp Med Biol 635, 7992.
222Maecker, HT, McCoy, JP & Nussenblatt, R (2012) Standardizing immunophenotyping for the Human Immunology Project. Nat Rev Immunol 12, 191200.
223McGuire, HM, Vogelzang, A, Ma, CS, et al. (2011) A subset of interleukin-21+ chemokine receptor CCR9+ T helper cells target accessory organs of the digestive system in autoimmunity. Immunity 34, 602615.
224Rodriguez, PC, Quiceno, DG & Ochoa, AC (2007) l-Arginine availability regulates T-lymphocyte cell-cycle progression. Blood 109, 15681573.
225Bettelli, E, Oukka, M & Kuchroo, VK (2007) T(H)-17 cells in the circle of immunity and autoimmunity. Nat Immunol 8, 345350.
226Duramad, P, McMahon, CW, Hubbard, A, et al. (2004) Flow cytometric detection of intracellular TH1/TH2 cytokines using whole blood: validation of immunologic biomarker for use in epidemiologic studies. Cancer Epidemiol Biomarkers Prev 13, 14521458.
227Jason, J & Larned, J (1997) Single-cell cytokine profiles in normal humans: comparison of flow cytometric reagents and stimulation protocols. J Immunol Methods 207, 1322.
228Miossec, P, Korn, T & Kuchroo, VK (2009) Interleukin-17 and type 17 helper T cells. N Engl J Med 361, 888898.
229Richard, N, Arnold, S, Hoeller, U, et al. (2011) Hydroxytyrosol is the major anti-inflammatory compound in aqueous olive extracts and impairs cytokine and chemokine production in macrophages. Planta Med 77, 18901897.
230Romagnani, S (1994) Lymphokine production by human T cells in disease states. Annu Rev Immunol 12, 227257.
231Maruyama, T, Mimura, K, Izawa, S, et al. (2011) Immunonutritional diet modulates natural killer cell activation and Th17 cell distribution in patients with gastric and esophageal cancer. Nutrition 27, 146152.
232Anikeeva, N & Sykulev, Y (2011) Mechanisms controlling granule-mediated cytolytic activity of cytotoxic T lymphocytes. Immunol Res 51, 183194.
233Issazadeh-Navikas, S, Teimer, R & Bockermann, R (2012) Influence of dietary components on regulatory T cells. Mol Med 18, 95110.
234Smyth, LJ, Starkey, C, Vestbo, J, et al. (2007) CD4-regulatory cells in COPD patients. Chest 132, 156163.
235Ukena, SN, Höpting, M, Velaga, S, et al. (2011) Isolation strategies of regulatory T cells for clinical trials: phenotype, function, stability, and expansion capacity. Exp Hematol 39, 11521160.
236Shevach, EM (2011) Biological functions of regulatory T cells. Adv Immunol 112, 137176.
237Campbell, DJ & Koch, MA (2011) Phenotypical and functional specialization of FOXP3+ regulatory T cells. Nat Rev Immunol 11, 119130.
238Bilate, AM & Lafaille, JJ (2012) Induced CD4+Foxp3+ regulatory T cells in immune tolerance. Annu Rev Immunol 30, 733758.
239Sanz, I, Wei, C, Lee, FE, et al. (2008) Phenotypic and functional heterogeneity of human memory B cells. Semin Immunol 20, 6782.
240Siekmann, JH, Allen, LH, Watnik, MR, et al. (2003) Titers of antibody to common pathogens: relation to food-based interventions in rural Kenyan schoolchildren. Am J Clin Nutr 77, 242249.
241van Riet, E, Retra, K, Adegnika, AA, et al. (2008) Cellular and humoral responses to tetanus vaccination in Gabonese children. Vaccine 26, 36903695.
242Chirumbolo, S (2012) Basophil activation test in allergy: time for an update? Int Arch Allergy Immunol 158, 99114.
243Beier-Holgersen, R & Brandstrup, B (2012) Influence of postoperative enteral nutrition on cellular immunity. A random double-blinded placebo controlled clinical trial. Int J Colorectal Dis 27, 513520.
244Jippo, T, Kobayashi, Y, Sato, H, et al. (2009) Inhibitory effects of guarana seed extract on passive cutaneous anaphylaxis and mast cell degranulation. Bioscience 73, 21102112.
245Mondello, S, Italiano, D, Giacobbe, MS, et al. (2010) Glutamine-supplemented total parenteral nutrition improves immunological status in anorectic patients. Nutrition 26, 677681.
246Lehuen, A & Novak, J (2011) Low numbers and altered phenotype of invariant natural killer T cells in recurrent varicella zoster virus infection. Cell Immunol 269, 7881.
247Larbi, A, Franceschi, C, Mazzatti, D, et al. (2008) Aging of the immune system as a prognostic factor for human longevity. Physiology (Bethesda) 23, 6474.
248Degauque, N, Boeffard, F, Foucher, Y, et al. (2011) The blood of healthy individuals exhibits CD8 T cells with a highly altered TCR Vb repertoire but with an unmodified phenotype. PLoS One 6, e21240.
249Noh, J & Noh, G (2012) Allergen-specific responses of CD19(high) and CD19(low) B cells in non-IgE-mediated food allergy of late eczematous reactions in atopic dermatitis: presence of IL-17- and IL-32-producing regulatory B cells (Br17 & Br32). Inflamm Allergy Drug Targets 11, 320329.
250Emerging Risk, FC, Kaptoge, S, Di Angelantonio, E, et al. (2010) C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis. Lancet 375, 132140.
251Erridge, C, Attina, T, Spickett, CM, et al. (2007) A high-fat meal induces low-grade endotoxemia: evidence of a novel mechanism of postprandial inflammation. Am J Clin Nutr 86, 12861292.
252Hingorani, AD, Shah, T, Casas, JP, et al. (2009) C-reactive protein and coronary heart disease: predictive test or therapeutic target? Clin Chem 55, 239255.
253Shah, T, Newcombe, P, Smeeth, L, et al. (2010) Ancestry as a determinant of mean population C-reactive protein values: implications for cardiovascular risk prediction. Circ Cardiovasc Genet 3, 436444.
254Renault, NK, Gaddipati, SR, Wulfert, F, et al. (2011) Multiple protein extract microarray for profiling human food-specific immunoglobulins A, M, G and E. J Immunol Methods 364, 2132.
255Anto, JM, Pinart, M, Akdis, M, et al. (2012) Understanding the complexity of IgE-related phenotypes from childhood to young adulthood: a Mechanisms of the Development of Allergy (MeDALL) seminar. J Allergy Clin Immunol 129, 943954.
256Bodtger, U, Assing, K & Poulsen, LK (2011) A prospective, clinical study on asymptomatic sensitisation and development of allergic rhinitis: high negative predictive value of allergological testing. Int Arch Allergy Immunol 155, 289296.
257Dekker, FW, Mulder Dzn, JD, Kramps, JA, et al. (1990) The Phadiatop in vitro test for allergy in general practice: is it useful? Fam Pract 7, 144148.
258Govaere, E, van Gysel, D, Verhamme, KM, et al. (2009) The association of allergic symptoms with sensitization to inhalant allergens in childhood. Pediatr Allergy Immunol 20, 448457.
259Lilja, G, Kusoffsky, E, Johansson, SG, et al. (1995) Screening of atopic allergy in 5-year-old children – a comparison of the diagnostic properties of Phadiatop Paediatric and Phadiatop. Allergy 50, 316321.
260Matricardi, PM, Nisini, R, Biselli, R, et al. (1994) Evaluation of the overall degree of sensitization to airborne allergens by a single serologic test: implications for epidemiologic studies of allergy. J Allergy Clin Immunol 93, 6879.
261Visness, CM, London, SJ, Daniels, JL, et al. (2009) Association of obesity with IgE levels and allergy symptoms in children and adolescents: results from the National Health and Nutrition Examination Survey 2005–2006. J Allergy Clin Immunol 123, 11631169, 1169.e1–1169.e4.
262Droste, JH, Kerhof, M, de Monchy, JG, et al. (1996) Association of skin test reactivity, specific IgE, total IgE, and eosinophils with nasal symptoms in a community-based population study. The Dutch ECRHS Group. J Allergy Clin Immunol 97, 922932.
263Kimmel, PL, Phillips, TM, Simmens, SJ, et al. (1998) Immunologic function and survival in hemodialysis patients. Kidney Int 54, 236244.
264Oberbach, A, Bluher, M, Wirth, H, et al. (2011) Combined proteomic and metabolomic profiling of serum reveals association of the complement system with obesity and identifies novel markers of body fat mass changes. J Proteome Res 10, 47694788.
265Matarese, G (2000) Leptin and the immune system: how nutritional status influences the immune response. Eur Cytokine Netw 11, 714.
266Mencarelli, A, Distrutti, E, Renga, B, et al. (2011) Probiotics modulate intestinal expression of nuclear receptor and provide counter-regulatory signals to inflammation-driven adipose tissue activation. PLoS One 6, e22978.
267Lash, GE & Pinto, LA (2010) Multiplex cytokine analysis technologies. Expert Rev Vaccines 9, 12311237.
268Richens, JL, Urbanowicz, RA, Metcalf, R, et al. (2010) Quantitative validation and comparison of multiplex cytokine kits. J Biomol Screen 15, 562568.
269Molet, S, Hamid, Q, Davoine, F, et al. (2001) IL-17 is increased in asthmatic airways and induces human bronchial fibroblasts to produce cytokines. J Allergy Clin Immunol 108, 430438.
270Raj, DSC, Shah, VO, Rambod, M, et al. (2009) Association of soluble endotoxin receptor CD14 and mortality among patients undergoing hemodialysis. Am J Kidney Dis 54, 10621071.
271Clifton, PM, Noakes, M, Keogh, J, et al. (2003) How effective are meal replacements for treating obesity? Asia Pac J Clin Nutr 12, Suppl., S51.
272Conde, J, Scotece, M, Gomez, R, et al. (2011) Adipokines: biofactors from white adipose tissue. A complex hub among inflammation, metabolism, and immunity. Biofactors 37, 413420.
273Conde, J, Scotece, M, Gómez, R, et al. (2010) At the crossroad between immunity and metabolism: focus on leptin. Expert Rev Clin Immunol 6, 801808.
274Faggioni, R, Feingold, KR & Grunfeld, C (2001) Leptin regulation of the immune response and the immunodeficiency of malnutrition. FASEB J 15, 25652571.
275Mackey-Lawrence, NM & Petri, WA Jr (2012) Leptin and mucosal immunity. Mucosal Immunol 5, 472479.
276Wilk, S, Scheibenbogen, C, Bauer, S, et al. (2011) Adiponectin is a negative regulator of antigen-activated T cells. Eur J Immunol 41, 23232332.
277Wu, CJ & Yu, ZR (2004) Effects on blood glucose, insulin, lipid and proatherosclerotic parameters in stable type 2 diabetic subjects during an oral fat challenge. Lipids Health Dis 3, 17.
278Mortensen, OH, Nielsen, AR, Erikstrup, C, et al. (2009) Calprotectin – a novel marker of obesity. PLoS One 4, e7419.
279Wassell, J (2011) Calprotectin testing in the community. Ann Clin Biochem 48, 12.
280Blum, S, Gunzinger, A, Muller, UR, et al. (2011) Influence of total and specific IgE, serum tryptase, and age on severity of allergic reactions to Hymenoptera stings. Allergy 66, 222228.
281Ludolph-Hauser, D, Rueff, F, Fries, C, et al. (2001) Constitutively raised serum concentrations of mast-cell tryptase and severe anaphylactic reactions to Hymenoptera stings. Lancet 357, 361362.
282Rueff, F, Przybilla, B, Bilo, MB, et al. (2010) Predictors of side effects during the buildup phase of venom immunotherapy for Hymenoptera venom allergy: the importance of baseline serum tryptase. J Allergy Clin Immunol 126, 105111.
283van Odijk, J, Peterson, CG, Ahlstedt, S, et al. (2006) Measurements of eosinophil activation before and after food challenges in adults with food hypersensitivity. Int Arch Allergy Immunol 140, 334341.
284de Kivit, S, Kraneveld, AD, Garssen, J, et al. (2011) Glycan recognition at the interface of the intestinal immune system: target for immune modulation via dietary components. Eur J Pharmacol 668, Suppl. 1, S124S132.
285Gorfu, G, Rivera-Nieves, J & Ley, K (2009) Role of beta integrins in intestinal lymphocyte homing and retention. Curr Mol Med 9, 836850.
286Steck-Scott, S, Arab, L, Craft, NE, et al. (2004) Plasma and lung macrophage responsiveness to carotenoid supplementation and ozone exposure in humans. Eur J Clin Nutr 58, 15711579.
287Taylor, DR (2011) Using biomarkers in the assessment of airways disease. J Allergy Clin Immunol 128, 927934.
288van der Top, EA, Perry, GA & Gentry-Nielsen, MJ (2006) A novel flow cytometric assay for measurement of in vivo pulmonary neutrophil phagocytosis. BMC Microbiol 6, 61.
289Vatrella, A, Bocchino, M, Perna, F, et al. (2007) Induced sputum as a tool for early detection of airway inflammation in connective diseases-related lung involvement. Respir Med 101, 13831389.
290Eksteen, B, Mora, JR, Haughton, EL, et al. (2009) Gut homing receptors on CD8 T cells are retinoic acid dependent and not maintained by liver dendritic or stellate cells. Gastroenterology 137, 320329.
291Gibson, RJ & Bowen, JM (2011) Biomarkers of regimen-related mucosal injury. Cancer Treat Rev 37, 487493.
292Langhorst, J, Elsenbruch, S, Koelzer, J, et al. (2008) Noninvasive markers in the assessment of intestinal inflammation in inflammatory bowel diseases: performance of fecal lactoferrin, calprotectin, and PMN-elastase, CRP, and clinical indices. Am J Gasterenterol 103, 162169.
293van Rheenen, PF, van de Vijver, E & Fidler, V (2010) Faecal calprotectin for screening of patients with suspected inflammatory bowel disease: diagnostic meta-analysis. BMJ 341, c3369.
294Hanson, LA, Bjorkander, J & Oxelius, VA (1983) Selective IgA deficiency. In Primary and Secondary Immunodeficiency Disorders, pp. 6264 [Chandra, RK, editor]. Edinburgh: Churchill Livingstone.
295Daele, J & Zicot, AF (2000) Humoral immunodeficiency in recurrent upper respiratory tract infections. Some basic, clinical and therapeutic features. Acta Otorhinolaryngol Belg 54, 373390.
296Bishop, NC & Gleeson, M (2009) Acute and chronic effects of exercise on markers of mucosal immunity. Front Biosci 14, 44444456.
297Costa, C, Rufino, R, Traves, SL, et al. (2008) CXCR3 and CCR5 chemokines in induced sputum from patients with COPD. Chest 133, 2633.
298Hacievliyagil, SS, Gunen, H, Mutlu, LC, et al. (2006) Association between cytokines in induced sputum and severity of chronic obstructive pulmonary disease. Respir Med 100, 846854.
299Klinder, A, Karlsson, PC, Clune, Y, et al. (2007) Fecal water as a non-invasive biomarker in nutritional intervention: comparison of preparation methods and refinement of different endpoints. Nutr Cancer 57, 158167.
300Long, KZ, Garcia, C, Ko, G, et al. (2011) Vitamin A modifies the intestinal chemokine and cytokine responses to norovirus infection in Mexican children. J Nutr 141, 957963.
301Mai, V, McCrary, QM, Sinha, R, et al. (2009) Associations between dietary habits and body mass index with gut microbiota composition and fecal water genotoxicity: an observational study in African American and Caucasian American volunteers. Nutr J 8, 49.
302Oberreuther-Moschner, DL, Jahreis, G, Rechkemmer, G, et al. (2004) Dietary intervention with the probiotics Lactobacillus acidophilus 145 and Bifidobacterium longum 913 modulates the potential of human faecal water to induce damage in HT29clone19A cells. Br J Nutr 91, 925932.
303Rechkemmer, G, Schnaebele, K, Bub, A, et al. (2002) Use of fecal water as a biomarker in dietary intervention studies. J Nutr 132, 3537S.
304Woods, JA, Dunne, C, Collins, JK, et al. (2002) Genotoxicity of fecal water in a free-living Irish population. Nutr Cancer 42, 6269.
305Di Pierro, F, Spinelli, G, Monsu, G, et al. (2011) Clinical effectiveness of a highly standardized and bioavailable mixture of flavonoids and triterpenes in the management of acute hemorroidal crisis. Acta Biomedica 82, 3540.
306Hamer, HM, Jonkers, DMAE, Renes, IB, et al. (2010) Butyrate enemas do not affect human colonic MUC2 and TFF3 expression. Eur J Gastroenterol Hepatol 22, 11341140.
307Linden, SK, Sutton, P, Karlsson, NG, et al. (2008) Mucins in the mucosal barrier to infection. Mucosal Immunol 1, 183197.