Journal
JOURNAL OF NEUROIMMUNOLOGY
Volume 125, Issue 1-2, Pages 134-140Publisher
ELSEVIER
DOI: 10.1016/S0165-5728(02)00018-8
Keywords
multiple sclerosis; IL-18; IL-12; IFN-gamma; CD40-CD40 ligand interactions
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We investigated T cell receptor induced IL-18 secretion, the cellular and molecular mechanism, associated with the induction of IL-18 and the role of IL-18 in IFN-gamma production in the different stages of multiple sclerosis (MS). We found that anti-CD3/CD28 induced IL-18 production by peripheral blood mononuclear cells was increased in both relapsing-remitting and secondary progressive MS. In controls and relapsing-remitting MS neutralizing anti-IL-12 and anti-IL-18 alone equally suppressed IFN-gamma production whereas in progressive MS, maximum suppression of IFN-gamma was only observed when neutralizing anti-IL-12 and anti-IL-18 were given together, suggesting that in progressive MS, IL-12 and IL-18 function in a non-linked manner to induce IFN-gamma, Elevated IL-18 production in MS was dependent on the interaction of antigen presenting cells with activated CD4(+) T cells via CD40-CD40 ligand and the levels of IL-18 correlated with disease duration in secondary progressive MS. These results demonstrated that IL-18 has an important role in augmenting Th-1 type immune responses in MS and may be involved in immune changes that occur when patients enter the progressive stage. (C) 2002 Published by Elsevier Science B.V.
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