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Defective Regulation Of IFN-gamma And IL-12 By Endogenous IL-10 In Progressive MS

Balashov KE, Comabella M, Ohashi T, Khoury SJ, Weiner HL
Neurology 2000 Jul 25;55(2):192-8
Harvard Medical School, Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA, USA
PMID# 10908889; UI# 20371003
Abstract

Background
MS is a chronic inflammatory disease of the CNS postulated to be a Th1 type Cell-mediated AutoImmune Disease. There is increased Interferon-gamma (IFN-gamma) secretion in MS, and IFN-gamma administration induces exacerbations of disease.

IFN-gamma expression is closely regulated by a number of Cytokines produced by different cells of the Immune System.

InterLeukin-12 (IL-12) is a major factor leading to Th1-type responses, including IFN-gamma secretion, and there is increased secretion of IL-12 in MS. IL-10 is a potent inhibitor of both IL-12 and IFN-gamma expression.

Methods
The authors investigated Cytokine production and proliferative responses of peripheral blood MonoNuclear Cells stimulated with soluble Anti-CD3 in healthy controls and patients with stable Relapsing/Remitting MS or Progressive MS.

Results
The authors found that T-Cell Receptor-mediated IFN-gamma and IL-10 secretion were increased in Progressive MS, whereas IL-4 and IL-2 secretion and Lymphocyte proliferative responses were normal.

Anti-IL-12 AntiBody suppressed raised IFN-gamma in Progressive MS but did not affect raised IL-10. In addition, neutralization of endogenous IL-10 upregulated IFN-gamma in controls but not Progressive MS.

IL-10 was produced by CD4+ cells whereas IFN-gamma was produced by both CD4+ and CD8+ cells. There were no differences in IL-10 Receptor expression in MS patients.

Conclusions
These abnormalities in IL-10 regulation were not seen in the Relapsing/Remitting form of MS.

Thus, the defect in regulation of both IL-12 and IFN-gamma production by endogenous IL-10 in Progressive MS could be an important factor involved in the transition of MS from the Relapsing to the Progressive stage and has implications for treating MS patients with exogenous IL-10.



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