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Brain cytokines and disease

  • Carlos R Plata-Salaman (a1)


Cytokines (e.g. various interleukins and subfamily members, tumor necrosis factors, interferons, chemokines and growth factors) act in the brain as immunoregulators and neuromodulators. Over a decade ago, the integrative article ‘Immunoregulators in the Nervous System’ (Neurosci Biobehav Rev 1991; 15: 185–215) provided a comprehensive framework of pivotal issues on cytokines and the nervous system that recently have been extensively studied. Cytokine profiles in the brain, including cytokine generation and action, have been studied in multiple models associated with neuropathophysiological conditions. These include: (1) acute conditions and disorders such as stroke (cerebral ischemia or infarction and intracranial hemorrhage), traumatic brain injury, spinal cord injury and acute neuropathies; (2) chronic neurodegenerative disorders and chronic conditions, including Alzheimer's disease, Parkinson's disease, neuropathic pain, epilepsy and chronic neuropathies; (3) brain infections, including bacterial meningitis and encephalitis; (4) brain tumors; (5) neuroimmunological disorders per se, such as multiple sclerosis; (5) psychiatric disorders, including schizophrenia and depression; (6) neurological and neuropsychiatric manifestations associated with non- central nervous system (CNS) disorders such as peripheral cancer, liver, kidney and metabolic compromise, and peripheral infectious and inflammatory conditions; and (7) cytokine immunotherapy, which can be accompanied by neuropsychiatric manifestations when administered either via peripheral or brain routes. Cytokine profiles have also been studied in multiple animal models challenged with inflammatory, infectious, chemical, malignant and stressor insults. Essentially data show that cytokines play a pivotal role in multiple neuropathophysiological processes associated with different types of disorders and insults. Cytokine expression and action in the brain shows a different profile across conditions, but some similarities exist. Under a defined temporal sequence, cytokine involvement in neuroprotection or the induction of a deleterious pathophysiological cascade and in resolution/healing is proposed depending on the type of cytokine. In the brain, functional interactions among cytokines, balance between pro-inflammatory and anti-inflammatory cytokines and functional interactions with neurotransmitters and neuropeptides play a pivotal role in the overall cytokine profile, pattern of neuropathophysiological cascades, and quality and magnitude of neuropsychiatric manifestations. In this brief review various selected cytokine-related issues with relevance to the brain are discussed.


Corresponding author

Carlos R. Plata-Salaman, DSc, MD, Johnson & Johnson Pharmaceutical Research and Development, Welsh and McKean Roads, Spring House, PA 19477–0776, USA; Tel: + 215-628-5849; Fax: + 215-540-4701; E-mail:


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1.Plata-Salaman, CR. Immunoregulators in the nervous system. Neurosci Biobehav Rev 1991;15: 185215.
2.Miyamoto, NG, Medberry, PS, Hesselgesser, J, Boehlk, S, Nelson, PJ, Krensky, AM, Perez, HD. Interleukin-1 induction of the chemokine RANTES promoter in the human astrocytoma line CH235 requires both constitutive and inducible transcription factors. J Neuroimmunol 2000;105: 7890.
3.Uehara, T, Matsuno, J, Kaneko, Met al. Transient nuclear factor kappaB (NF-kappaB) activation stimulated by interleukin-1β may be partly dependent on proteasome activity, but not phosphorylation and ubiquitination of the IkappaBalpha molecule, in C6 glioma cells. Regulation of NF-kappaB linked to chemokine production. J Biol Chem 1999;274: 15 875–15 882.
4.Gayle, D, Ilyin, SE, Miele, ME, Plata-Salaman, CR. Modulation of TNF-alpha mRNA production in rat C6 glioma cells by TNF-alpha, IL-1 beta, IL-6, and IFN-alpha: in vitro analysis of cytokine–cytokine interactions. Brain Res Bull 1998;47: 231235.
5.Tchirkov, A, Rolhion, C, Bertrand, S, Dore, JF, Dubost, JJ, Verrelle, P. IL-6 gene amplification and expression in human glioblastomas. Br J Cancer 2001;85: 518522.
6.Malaplate-Armand, C, Gueguen, Y, Bertrand, P, Ferrari, L, Batt, AM. U373-MG response to interleukin-1β-induced oxidative stress. Cell Biol Toxicol 2000;16: 155163.
7.Meini, A, Benocci, A, Frosini, Met al. Nitric oxide modulation of interleukin-1[β]-evoked intracellular Ca2+ release in human astrocytoma U-373 MG cells and brain striatal slices. J Neurosci 2000;20: 89808986.
8.Pita, I, Jelaso, AM, Ide, CF. IL-1β increases intracellular calcium through an IL-1 type 1 receptor mediated mechanism in C6 astrocytic cells. Int J Dev Neurosci 1999;17: 813820.
9.Schumann, G, Fiebich, BL, Menzel, D, Hull, M, Butcher, R, Nielsen, P, Bauer, J. Cytokine-induced transcription of protein-tyrosine-phosphatases in human astrocytoma cells. Mol Brain Res 1998;62: 5664.
10.Esteve, PO, Tremblay, P, Houde, M, St-Pierre, Y, Mandeville, R. In vitro expression of MMP-2 and MMP-9 in glioma cells following exposure to inflammatory mediators. Biochim Biophys Acta 1998;1403: 8596.
11.Nishiya, T, Uehara, T, Kaneko, M, Nomura, Y. Involvement of nuclear factor-kappaB (NF-kappaB) signaling in the expression of inducible nitric oxide synthase (iNOS) gene in rat C6 glioma cells. Biochem Biophys Res Commun 2000;275: 268273.
12.Brivanlou, AH, Darnell, JE Jr.Signal transduction and the control of gene expression. Science 2002;295: 813818.
13.Pousset, F, Dantzer, R, Kelley, KW, Parnet, P. Interleukin-1 signaling in mouse astrocytes involves Akt. a study with interleukin-4 and IL-10. Eur Cytokine Netw 2000;11: 427434.
14.Vann, LR, Payne, SG, Edsall, LC, Twitty, S, Spiegel, S, Milstien, S. Involvement of sphingosine kinase in TNF-a stimulated tetrahydrobiopterin biosynthesis in C6 glioma cells. J Biol Chem 2002: 28.
15.Ilyin, SE, Gayle, D, González-Gómez, I, Miele, ME, Plata-Salaman, CR. Brain tumor development in rats is associated with changes in central nervous system cytokine and neuropeptide systems. Brain Res Bull 1999;48: 363373.
16.Ilyin, SE, González-Gómez, I, Gilles, FH, Plata-Salaman, CR. Interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-1 receptor type I, IL-1 receptor antagonist and TGF-beta 1 mRNAs in pediatric astrocytomas, ependymomas and primitive neuroectodermal tumors. Mol Chem Neuropathol 1998;33: 125137.
17.Sasaki, A, Ishiuchi, S, Kanda, T, Hasegawa, M, Nakazato, Y. Analysis of interleukin-6 gene expression in primary human gliomas, glioblastoma xenografts, and glioblastoma cell lines. Brain Tumor Pathol 2001;18: 1321.
18.Sasaki, A, Tamura, M, Hasegawa, M, Ishiuchi, S, Hirato, J, Nakazato, Y. Expression of interleukin-1β mRNA and protein in human gliomas assessed by RT-PCR and immunohistochemistry. J Neuropathol Exp Neurol 1998;57: 653663.
19.Ilyin, SE, Gonzalez-Gomez, I, Romanovicht, A, Gayle, D, Gilles, FH, Plata-Salaman, CR. Autoregulation of the interleukin-1 system and cytokine–cytokine interactions in primary human astrocytoma cells. Brain Res Bull 2000;51: 2934.
20.Dunn, IF, Heese, O, Black, PM. Growth factors in glioma angiogenesis. FGFs, PDGF, EGF, and TGFs. J Neurooncol 2000;50: 121137.
21.Platten, M, Wick, W, Weller, M. Malignant glioma biology. role for TGF-β in growth, motility, angiogenesis, and immune escape. Microsc Res Tech 2001;52: 401410.
22.Zagzag, D, Friedlander, DR, Margolis, Bet al. Molecular events implicated in brain tumor angiogenesis and invasion. Pediatr Neurosurg 200l;33: 4955.
23.Dinarello, CA. Interleukin-1, interleukin-1 receptors and interleukin-1 receptor antagonist. Int Rev Immunol 1998;16: 457499.
24.Castigli, E, Arcuri, C, Giovagnoli, Let al. Interleukin-1β induces apoptosis in GL15 glioblastoma-derived human cell line. Am J Physiol 2000;279: C2043C2049.
25.Oelmann, E, Kraemer, A, Serve, Het al. Autocrine interleukin-1 receptor antagonist can support malignant growth of glioblastoma by blocking growth-inhibiting autocrine loop of interleukin-1. Int J Cancer 1997;71: 10661076.
26.Hayashi, S, Yamamoto, M, Ueno, Yet al. Expression of nuclear factor-kappa B, tumor necrosis factor receptor type 1, and c-Myc in human astrocytomas. Neurol Med Chir 2001;41: 187195.
27.Fathallah-Shaykh, HM, Zhao, LJ, Mickey, B, Kafrouni, AI. Molecular advances to treat cancer of the brain. Expert Opin Invest Drugs 2000;9: 12071215.
28.Plata-Salaman, CR, Ilyin, SE, Gayle, D, Flynn, MC. Gram-negative and Gram-positive bacterial products induce differential cytokine profiles in the brain: Analysis using an integrative molecular-behavioral in vivo model. Int J Mol Med 1998;1: 387397.
29.Turrin, NP, Gayle, D, Ilyin, SEet al. Pro-inflammatory and anti-inflammatory cytokine mRNA induction in the periphery and brain following intraperitoneal administration of bacterial lipopolysaccharide. Brain Res Bull 2001;54: 443453.
30.Frieling, JTM, Mulder, JA, Hendriks, T, Curfs, JHAJ, Vanderlinden, CJ, Sauerwein, RW. Differential induction of pro- and anti-inflammatory cytokines in whole blood by bacteria: effects of antibiotic treatment. Antimicrobial Agents Chemother 1997;41: 14391443.
31.Kragsbjerg, P, Holmberg, H, Vikerfors, T. Dynamics of blood cytokine concentrations in patients with bacteremic infections. Scand J Infect Dis 1996;28: 391398.
32.Gayle, D, Ilyin, SE, Plata-Salaman, CR. Feeding status and bacterial LPS-induced cytokine and neuropeptide gene expression in the hypothalamus. Am J Physiol 1999;277: R1188R1195.
33.Gayle, D, Ilyin, SE, Flynn, MC, Plata-Salaman, CR. Lipopolysaccharide (LPS)- and muramyl dipeptide (MDP)-induced anorexia during refeeding following acute fasting: characterization of brain cytokine and neuropeptide systems mRNAs. Brain Res 1998;795: 7786.
34.Plata-Salaman, CR, Turrin, NP. Cytokine interactions and cytokine balance in the brain: Relevance to neurology and psychiatry. Mol Psychiatry 1999;4: 303306.
35.Ossege, LM, Sindern, E, Voss, B, Malin, J-P. Expression of tumor necrosis factor-a and transforming growth factor-β1 in cerebrospinal fluid cells in meningitis. J Neurol Sci 1996;144: 113.
36.López-Cortés, LF, Cruz-Ruiz, M, Gómez-Mateos, J, Jiménez-Hernández, D, Palomino, J, Jiménez, E. Measurement of levels of tumor necrosis factor-a and interleukin-1β in the CSF of patients with meningitis of different etiologies: utility in the differential diagnosis. Clin Infect Dis 1993;16: 534539.
37.Ohga, S, Aoki, T, Okada, Ket al. Cerebrospinal fluid concentrations of interleukin-1β, tumour necrosis factor-a, and interferon gamma in bacterial meningitis. Arch Dis Childhood 1994;70: 123125.
38.Akalin, H, Akdis, AC, Mistik, R, Helvaci, S, Kilicturgay, K. Cerebrospinal fluid interleukin-1β/interleukin-1 receptor antagonist balance and tumor necrosis factor-a concentrations in tuberculous, viral and acute bacterial meningitis. Scand J Infect Dis 1994;26: 667674.
39.Van Deuren, M, Van Der Ven-Jongekrijg, J, Bartelink, AKM, Van Dalen, R, Sauerwein, R W, Van Der Meer, J WM. Correlation between proinflammatory cytokines and anti-inflammatory mediators and the severity of disease in meningococcal infections. J Infect Dis 1995;172: 433439.
40.Glimåker, M, Kragsbjerg, P, Forsgren, M, Olcén, P. Tumor necrosis factor-α (TNFα) in cerebrospinal fluid from patients with bacterial meningitis of different etiologies: High levels of TNFα indicate bacterial meningitis. J Infect Dis 1993;167: 882889.
41.Frei, K, Piani, D, Pfister, HW, Fontana, A. Immune-mediated injury in bacterial meningitis. Int Rev Exp Pathol 1993;34B: 183192.
42.Briese, T, Schneemann, A, Lewis, AJet al. Genomic organization of Borna disease virus. Proc Natl Acad Sci USA 1994;91: 43624366.
43.Cubitt, B, Oldstone, C, De La Torre, JC. Sequence and genome organization of Borna disease virus. J Virol 1994;68: 13821396.
44.Schneider, PA, Schneemann, A, Lipkin, WI. RNA splicing in Borna disease virus, a nonsegmented, negative-strand RNA virus. J Virol 1994;68: 50075012.
45.Carbone, KM, Duchala, CS, Griffin, JW, Kincaid, AL, Narayan, O. Pathogenesis of Borna disease in rats: Evidence that intra-axonal spread is the major route for virus dissemination and the determinant for disease incubation. J Virol 1987;61: 34313440.
46.Carbone, KM, Trapp, BD, Griffin, JW, Duchala, CS, Narayan, O. Astrocytes and Schwann cells are virus-host cells in the nervous system of rats with Borna disease. J Neuropathol Exp Neurol 1989;48: 631644.
47.Carbone, KM, Moench, TR, Lipkin, WI. Borna disease virus replicates in astrocytes, Schwann cells and ependymal cells in persistently infected rats: Location of viral genomic and messenger RNAs by in situ hybridization. J Neuropathol Exp Neurol 1991;50: 205214. la Torre, JC, Gonzalez-Dunia, D, Cubitt, Bet al. Detection of Borna disease virus antigen and RNA in human autopsy brain samples from neuropsychiatric patients. Virology 1996;223: 272282.
49.Durrwald, R, Ludwig, H. Borna disease virus (BDV), a (zoonotic?) worldwide pathogen. A review of the history of the disease and the virus infection with comprehensive bibliography. Zentralbl Veterinarmed 1997;B44: 147184.
50.Gonzalez-Dunia, D, Sauder, C, De La Torre, JC. Borna disease virus and the brain. Brain Res Bull 1997;44: 647664.
51.Rott, R, Becht, H. Natural and experimental Borna disease in animals. Curr Top Microbiol Immunol 1995;190: 1730.
52.Stitz, L, Dietzschold, B, Carbone, KM. Immunopathogenesis of Borna disease. Curr Top Microbiol Immunol 1995;190: 7592.
53.Shankar, V, Kao, M, Hamir, AN, Sheng, H, Koprowski, H, Dietzschold, B. Kinetics of virus spread and changes in levels of several cytokine mRNAs in the brain after intranasal infection of rats with Borna disease virus. J Virol 1992;66: 992998.
54.Hirano, N, Kao, M, Ludwig, H. Persistent, tolerant, or subacute infection in Borna disease virus-infected rats. J General Virol 1983;72: 15211530.
55.Narayan, O, Herzog, S, Frese, K, Scheefers, H, Rott, R. Behavioral disease in rats caused by immunopathological responses to persistent Borna virus in the brain. Science 1983;220: 14011403.
56.Sauder, C, De La Torre, JC. Cytokine expression in the rat central nervous system following perinatal Borna disease virus infection. J Neuroimmunol 1999;96: 2945.
57.Bautista, JR, Rubin, SA, Moran, TH, Schwartz, GJ, Carbone, KM. Developmental injury to the cerebellum following perinatal Borna disease virus infection. Dev Brain Res 1995;90: 4553.
58.Carbone, KM, Park, SW, Rubin, SA, Waltrip, IIRW, Vogelsang, GB. Borna disease: Association with a maturation defect in the cellular immune response. J Virol 1991;65: 61546164.
59.Plata-Salaman, CR, Ilyin, SE, Gayle, D, Romanovitch, A, Carbone, KM. Persistent Borna disease virus infection of neonatal rats causes brain regional changes of mRNAs for cytokines, cytokine receptor components and neuropeptides. Brain Res Bull 1999;49: 441451.
60.Balasingam, V, Tejada-Berges, T, Wright, E, Bouckova, R, Yong, VW. Reactive astrogliosis in the neonatal mouse brain and its modulation by cytokines. J Neurosci 1994;14: 846856.
61.Yong, VW. Cytokines, astrogliosis, and neurotrophism following CNS trauma. In: Ransohoff, RM, Benveniste, EN, eds. Cytokines and the CNS. Boca Raton: CRC Press, 1996: 309327.
62.Plata-Salaman, CR. Brain mechanisms in cytokine-induced anorexia. Psychoneuroendocrinology 1999;24: 2541.
63.Plata-Salaman, CR. Anorexia during acute and chronic disease: Relevance of neurotransmitter-peptide–cytokine interactions. Nutrition 1997;13: 159160.
64.Dunn, AJ, Wang, J, Ando, T. Effects of cytokines on cerebral neurotransmission. Comparison with the effects of stress. Adv Exp Med Biol 1999;461: 117127.
65.Mohankumar, SM, Mohankumar, PS, Quadri, SK. Lipopolysaccharide-induced changes in monoamines in specific areas of the brain: blockade by interleukin-1 receptor antagonist. Brain Res 1999;824: 232237.
66.Zumwalt, JW, Thunstrom, BJ, Spangelo, BL. Interleukin-1β and catecholamines synergistically stimulate interleukin-6 release from rat C6 glioma cells in vitro: a potential role for lysophosphatidylcholine. Endocrinology 1999;140: 888896.
67.Turnbull, AV, Rivier, CL. Regulation of the hypothalamic–pituitary–adrenal axis by cytokines: actions and mechanisms of action. Physiol Rev 1999;79: 171.
68.Sonti, G, Ilyin, SE, Plata-Salaman, CR. Neuropeptide Y blocks and reverses interleukin-1 beta-induced anorexia in rats. Peptides 1996;17: 517520.
69.Turrin, NP, Plata-Salaman, CR. Cytokine–cytokine interactions in the brain. Brain Res Bull 2000;51: 39.
70.Thibeault, I, Laflamme, N, Rivest, S. Regulation of the gene encoding the monocyte chemoattractant protein 1 (MCP-1) in the mouse and rat brain in response to circulating LPS and pro-inflammatory cytokines. J Comp Neurol 2001;434: 461477.
71.Minghetti, L, Walsh, DT, Levi, G, Perry, VH. In vivo expression of cyclooxygenase-2 in rat brain following intraparenchymal injection of bacterial endotoxin and inflammatory cytokines. J Neuropathol Exp Neurol 1999;58: 11841191.
72.Laflamme, N, Lacroix, S, Rivest, S. An essential role of interleukin-1beta in mediating NF-kappaB activity and COX-2 transcription in cells of the blood–brain barrier in response to a systemic and localized inflammation but not during endotoxemia. J Neurosci 1999;19: 1092310930.
73.Plata-Salaman, CR, Ilyin, SE, Turrin, NPet al. Kindling modulates the IL-1 beta system, TNF-alpha, TGF-beta 1 and neuropeptide mRNAs in specific brain regions. Mol Brain Res 2000;75: 248258.
74.Feuerstein, GZ, Wang, X, Barone, FC. The role of cytokines in the neuropathology of stroke and neurotrauma. Neuroimmunomodulation 1998;5: 143159.
75.Mrak, RE, Griffin, WS. Interleukin-1, neuroinflammation, and Alzheimer's disease. Neurobiol Aging 2001;22: 903908.
76.Akiyama, H, Barger, S, Barnum, Set al. Inflammation in Alzheimer's Disease. Neurobiol Aging 2000;21: 383421.
77.Hayley, S, Lacosta, S, Merali, Z, Van Rooijen, N, Anisman, H. Central monoamine and plasma corticosterone changes induced by a bacterial endotoxin: sensitization and cross-sensitization effects. Eur J Neurosci 2001;13: 11551165.
78.Stern, EL, Quan, N, Proescholdt, MG, Herkenham, M. Spatiotemporal induction patterns of cytokine and related immune signal molecule mRNAs in response to intrastriatal injection of lipopolysaccharide. J Neuroimmunol 2000;109: 245260.
79.Allan, SM, Harrison, DC, Read, Set al. Selective increases in cytokine expression in the rat brain in response to striatal injection of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate and interleukin-1. Brain Res Mol Brain Res 2001;93: 180189.
80.Eriksson, C, Nobel, S, Winblad, B, Schultzberg, M. Expression of interleukin 1 alpha and beta, and interleukin 1 receptor antagonist mRNA in the rat central nervous system after peripheral administration of lipopolysaccharides. Cytokine 2000;12: 423431.
81.Quan, N, Whiteside, M, Herkenham, M. Time course and localization patterns of interleukin-1β messenger RNA expression in brain and pituitary after peripheral administration of lipopolysaccharide. Neuroscience 1998;83: 281293.
82.van Dam, AM, Poole, S, Schultzberg, M, Zavala, F, Tilders, FJ. Effects of peripheral administration of LPS on the expression of immunoreactive interleukin-1 alpha, beta, and receptor antagonist in rat brain. Ann NY Acad Sci 1998;840: 128138.
83.Laye, S, Gheusi, G, Cremona, Set al. Endogenous brain IL-1 mediates LPS-induced anorexia and hypothalamic cytokine expression. Am J Physiol 2000;279: R93R98.
84.Hansen, MK, Nguyen, KT, Goehler, LEet al. Effects of vagotomy on lipopolysaccharide-induced brain interleukin-1beta protein in rats. Auton Neurosci 2000;85: 119126.
85.Cartmell, T, Luheshi, GN, Rothwell, NJ. Brain sites of action of endogenous interleukin-1 in the febrile response to localized inflammation in the rat. J Physiol 1999;518: 585594.
86.Plata-Salaman, CR, Ilyin, SE, Gayle, D. Brain cytokine mRNAs in anorectic rats bearing prostate adenocarcinoma tumor cells. Am J Physiol 1998;275: R566R573.
87.Plata-Salaman, CR. Brain cytokine production and action in anorexia and cachexia. Cytokine 2001;15: 13.
88.Laviano, A, Renvyle, T, Meguid, MM, Yang, ZJ, Cangiano, C, Rossi-Fanelli, F. Relationship between interleukin-1 and cancer anorexia. Nutrition 1995;11 (Suppl.):680683.
89.Wang, W, Lonnroth, C, Svanberg, E, Lundholm, K. Cytokine and cyclooxygenase-2 protein in brain areas of tumor-bearing mice with prostanoid-related anorexia. Cancer Res 2001;61: 47074715.
90.Negri, DR, Mezzanzanica, D, Sacco, Set al. Role of cytokines in cancer cachexia in a murine model of intracerebral injection of human tumours. Cytokine 2001;15: 2738.
91.Sonti, G, Ilyin, SE, Plata-Salaman, CR. Anorexia induced by cytokine interactions at pathophysiological concentrations. Am J Physiol 1996;270: R1394R1402.
92.Aloisi, F, De Simone, R, Columba-Cabezas, S, Levi, G. Opposite effects of interferon-gamma and prostaglandin E2 on tumor necrosis factor and interleukin-10 production in microglia: a regulatory loop controlling microglia pro- and anti-inflammatory activities. J Neurosci Res 1999;56: 571580.
93.Zhang, J, Rivest, S. Anti-inflammatory effects of prostaglandin E2 in the central nervous system in response to brain injury and circulating lipopolysaccharide. J Neurochem 2001;76: 855864.
94.Meager, T. Overview (a), Cytokine action (b), In vivo properties of cytokines, (c) Cytokines and pathology (d). In: James, K, Morris, A, eds. The Molecular Biology of Cytokines. New York: John Wiley & Sons, 1998: 121, 111–140, 181–214, 215–236.
95.Perini, F, Morra, M, Alecci, M, Galloni, E, Marchi, M, Toso, V. Temporal profile of serum anti-inflammatory and pro-inflammatory interleukins in acute ischemic stroke patients. Neurol Sci 2001;22: 289296.
96.van Deuren, M, van Der Ven-Jongekrijg, J, Vannier, Eet al. The pattern of interleukin-1β (IL-1β) and its modulating agents IL-1 receptor antagonist and IL-1 soluble receptor type II in acute meningococcal infections. Blood 1997;90: 11011108.
97.Mikuniya, T, Nagai, S, Takeuchi, Met al. Significance of the interleukin-1 receptor antagonist/interleukin-1β ratio as a prognostic factor in patients with pulmonary sarcoidosis. Respiration 2000;67: 389396.
98.Donnelly, SC, Strieter, RM, Reid, PTet al. The association between mortality rates and decreased concentrations of interleukin-10 and interleukin-1 receptor antagonist in lung fluids of patients with the adult respiratory distress syndrome. Ann Int Med 1996;125: 191196.
99.Teppo, AM, Honkanen, E, Ahonen, J, Gronhagen-Riska, C. Does increased urinary interleukin-1 receptor antagonist/interleukin-1β ratio indicate good prognosis in renal transplant recipients? Transplantation 1998;66: 10091014.
100.Holdsworth, SR, Kitching, AR, Tipping, PG. Th1 and Th2 T helper cell subsets affect patterns of injury and outcomes in glomerulonephritis. Kidney Int 1999;55: 11981216.
101.Lim, CS, Zheng, S, Kim, YSet al. Th1/Th2 predominance and pro-inflammatory cytokines determine the clinicopathological severity of IgA nephropathy. Nephrol Dial Transplant 2001;16: 269275.
102.Kurzrock, R. Cytokine deregulation in cancer. Biomed Pharmacother 2001;55: 543547.
103.Oliver, SJ. The Th1/Th2 paradigm in the pathogenesis of scleroderma, and its modulation by thalidomide. Curr Rheumatol Rep 2000;2: 486491.
104.Verhoef, CM, Van Roon, JA, Vianen, MEet al. Mutual antagonism of rheumatoid arthritis and hay fever;a role for type 1/type 2 T cell balance. Ann Rheum Dis 1998;57: 275280.
105.Shimauchi, H, Takayama, S, Imai-Tanaka, T, Okada, H. Balance of interleukin-1β and interleukin-1 receptor antagonist in human periapical lesions. J Endod 1998;24: 116119.
106.Plata-Salaman, CR. Cytokine action in the nervous system at pathophysiological versus pharmacological concentrations. Adv Exp Med Biol 1996;402: 191197.
107.Ilyin, SE, Sonti, G, Gayle, D, Plata-Salaman, CR. Regulation of brain interleukin-1 beta (IL-1 beta) system mRNAs in response to pathophysiological concentrations of IL-1 beta in the cerebrospinal fluid. J Mol Neurosci 1996;7: 169181.
108.Woiciechowsky, C, Asadullah, K, Nestler, Det al. Sympathetic activation triggers systemic interleukin-10 release in immunodepression induced by brain injury. Nature Med 1998;4: 808813.
109.Plata-Salaman, CR. Brain injury and immunosuppression. Nature Med 1998;4: 768769.
110.Krueger, JM, Fang, J, Taishi, P, Chen, Z, Kushikata, T, Gardi, J. Sleep. A physiologic role for IL-1 beta and TNF-alpha. Ann N Y Acad Sci 1998;856: 148159.
111.Pabst, MJ, Beranova-Giorgianni, S, Krueger, JM. Effects of muramyl peptides on macrophages, monokines, and sleep. Neuroimmunomodulation 1999;6: 261283.
112.Kluger, MJ, Kozak, W, Leon, LR, Soszynski, D, Conn, CA. Cytokines and fever. Neuroimmunomodulation 1995;2: 216223.
113.Elmquist, JK, Scammell, TE, Saper, CB. Mechanisms of CNS response to systemic immune challenge: the febrile response. Trends Neurosci 1997;20: 565570.
114.Maes, M, Bosmans, E, Calabrese, J, Smith, R, Meltzer, H Y. Interleukin-2 and interleukin-6 in schizophrenia and mania: effects of neuroleptics and mood stabilizers. J Psychiatr Res 1995;29: 141152.
115.Dinarello, CA, Pomerantz, BJ. Proinflammatory cytokines in heart disease. Blood Purif 2001;19: 314321.
116.Plata-Salaman, CR, Wilson, CD, Ffrench-Mullen, J MH. In vivo IL-1β-induced modulation of G-protein a O subunit subclass in the hypothalamic ventromedial nucleus: Implications to IL-1β-associated anorexia. Mol Brain Res 1998;58: 188194.



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