IL-18 is linked to raised IFN-γ in multiple sclerosis and is induced by activated CD4+ T cells via CD40-CD40 ligand interactions

Arnon Karni, Djordje N. Koldzic, Padmanabhan Bharanidharan, Samia J. Khoury, Howard L. Weiner

Research output: Contribution to journalArticlepeer-review

Abstract

We investigated T cell receptor induced IL-18 secretion, the cellular and molecular mechanisms associated with the induction of IL-18 and the role of IL-18 in IFN-γ 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-γ production whereas in progressive MS, maximum suppression of IFN-γ 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-γ. 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.

Original languageEnglish
Pages (from-to)134-140
Number of pages7
JournalJournal of Neuroimmunology
Volume125
Issue number1-2
DOIs
StatePublished - 2002
Externally publishedYes

Keywords

  • CD40-CD40 ligand interactions
  • IFN-γ
  • IL-12
  • IL-18
  • Multiple sclerosis

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