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The Journal of Immunology, Vol 149, Issue 7 2496-2505, Copyright © 1992 by American Association of Immunologists
ARTICLES |
MK Kennedy, DS Torrance, KS Picha and KM Mohler
Department of Immunology, Immunex Corporation, Seattle, WA 98101.
Experimental autoimmune encephalomyelitis (EAE) serves as an important animal model for understanding the events that lead to immune-mediated inflammation and tissue destruction within the central nervous system. We have utilized a murine adoptive transfer model of EAE and semiquantitative reverse transcriptase-polymerase chain reaction analysis to examine cytokine mRNA expression within the central nervous system in relation to the onset and resolution of paralysis associated with EAE. Spinal cord samples, obtained from mice as they progressed through discrete clinical stages of EAE, were examined for the expression of six cytokine genes (IL-1 alpha, IL-2, IL-4, IL-6, IL-10, and IFN-gamma). Distinct patterns of cytokine gene expression were observed during the acute, recovery, and chronic phases of EAE. The acute phase of disease was characterized by rapid increases in the levels of mRNA for IL-2, IL-4, IL-6, IFN-gamma, and IL-1 alpha. In fact, peak expression of several cytokine mRNA (e.g., IL-2, IL-4, IL-6, and IFN-gamma) occurred before the peak in clinical severity. In contrast, IL-1 alpha mRNA levels were elevated throughout the initial disease course. IL-10 mRNA demonstrated only modest increases during the acute phase of EAE. Stabilization of the clinical symptoms was characterized by rapid declines in the mRNA levels of IL-2, IL-4, IL-6, and IFN-gamma. The decreases in these four cytokine mRNA levels occurred concomitant with a dramatic rise in IL-10 mRNA. Finally, of the six cytokine mRNA examined, only IL-1 alpha, IFN-gamma, and IL-10 mRNA remained elevated during the early chronic stage. These results suggest that local cytokine production varies significantly during the course of EAE and that increases in discrete sets of cytokines are associated with the acute response and the recovery/chronic phase of disease.
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J. L. Croxford, K. Triantaphyllopoulos, O. L. Podhajcer, M. Feldmann, D. Baker, and Y. Chernajovsky Cytokine Gene Therapy in Experimental Allergic Encephalomyelitis by Injection of Plasmid DNA-Cationic Liposome Complex into the Central Nervous System J. Immunol., May 15, 1998; 160(10): 5181 - 5187. [Abstract] [Full Text] [PDF] |
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M. Arnush, A. L. Scarim, M. R. Heitmeier, C. B. Kelly, and J. A. Corbett Potential Role of Resident Islet Macrophage Activation in the Initiation of Autoimmune Diabetes J. Immunol., March 15, 1998; 160(6): 2684 - 2691. [Abstract] [Full Text] [PDF] |
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S. A. Stohlman, C. C. Bergmann, M. T. Lin, D. J. Cua, and D. R. Hinton CTL Effector Function Within the Central Nervous System Requires CD4+ T Cells J. Immunol., March 15, 1998; 160(6): 2896 - 2904. [Abstract] [Full Text] [PDF] |
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B. M. Segal, B. K. Dwyer, and E. M. Shevach An Interleukin (IL)-10/IL-12 Immunoregulatory Circuit Controls Susceptibility to Autoimmune Disease J. Exp. Med., February 16, 1998; 187(4): 537 - 546. [Abstract] [Full Text] [PDF] |
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A. Raisanen-Sokolowski, T. Glysing-Jensen, P. L. Mottram, and M. E Russell Sustained Anti-CD4/CD8 Treatment Blocks Inflammatory Activation and Intimal Thickening in Mouse Heart Allografts Arterioscler. Thromb. Vasc. Biol., October 1, 1997; 17(10): 2115 - 2122. [Abstract] [Full Text] |
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R. Aharoni, D. Teitelbaum, M. Sela, and R. Arnon Copolymer 1 induces T cells of the T helper type 2 that crossreact with myelin basic protein and suppress experimental autoimmune encephalomyelitis PNAS, September 30, 1997; 94(20): 10821 - 10826. [Abstract] [Full Text] [PDF] |
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S. Marusic and S. Tonegawa Tolerance Induction and Autoimmune Encephalomyelitis Amelioration After Administration of Myelin Basic Protein-derived Peptide J. Exp. Med., August 18, 1997; 186(4): 507 - 515. [Abstract] [Full Text] [PDF] |
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P. M. Mathisen, M. Yu, J. M. Johnson, J. A. Drazba, and V. K. Tuohy Treatment of Experimental Autoimmune Encephalomyelitis with Genetically Modified Memory T Cells J. Exp. Med., July 7, 1997; 186(1): 159 - 164. [Abstract] [Full Text] [PDF] |
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M. Rostworowski, V. Balasingam, S. Chabot, T. Owens, and V. W. Yong Astrogliosis in the Neonatal and Adult Murine Brain Post-Trauma: Elevation of Inflammatory Cytokines and the Lack of Requirement for Endogenous Interferon-gamma J. Neurosci., May 15, 1997; 17(10): 3664 - 3674. [Abstract] [Full Text] [PDF] |
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Y Chen, V. Kuchroo, J Inobe, D. Hafler, and H. Weiner Regulatory T cell clones induced by oral tolerance: suppression of autoimmune encephalomyelitis Science, August 26, 1994; 265(5176): 1237 - 1240. [Abstract] [PDF] |
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E. A. Eugenin, D. Eckardt, M. Theis, K. Willecke, M. V. L. Bennett, and J. C. Saez Microglia at brain stab wounds express connexin 43 and in vitro form functional gap junctions after treatment with interferon-gamma and tumor necrosis factor-alpha PNAS, March 27, 2001; 98(7): 4190 - 4195. [Abstract] [Full Text] [PDF] |
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