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-) secretion in MS, and IFN- administration induces exacerbations of disease.
IFN- 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- secretion, and there is increased secretion of IL-12 in MS. IL-10 is a potent inhibitor of both IL-12 and IFN- expression.
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.
The authors found that T-Cell Receptor-mediated IFN- 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- in Progressive MS but did not affect raised IL-10. In addition, neutralization of endogenous IL-10 upregulated IFN- in controls but not Progressive MS.
IL-10 was produced by CD4+ cells whereas IFN- was produced by both CD4+ and CD8+ cells. There were no differences in IL-10 Receptor expression in MS patients.
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- 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.