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

J Neuroimmunol. 2002 Apr;125(1-2):134-40. doi: 10.1016/s0165-5728(02)00018-8.


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-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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • CD28 Antigens / immunology
  • CD3 Complex / immunology
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / metabolism*
  • CD40 Antigens / metabolism*
  • CD40 Ligand / metabolism*
  • Cells, Cultured
  • Female
  • Humans
  • Interferon-gamma / biosynthesis*
  • Interferon-gamma / immunology
  • Interleukin-12 / immunology
  • Interleukin-18 / biosynthesis*
  • Interleukin-18 / immunology
  • Interleukin-18 / metabolism
  • Interleukin-18 Receptor alpha Subunit
  • Lymphocyte Activation / immunology
  • Male
  • Middle Aged
  • Multiple Sclerosis / immunology*
  • Multiple Sclerosis / metabolism
  • Receptors, Interleukin / biosynthesis
  • Receptors, Interleukin-18


  • CD28 Antigens
  • CD3 Complex
  • CD40 Antigens
  • IL18R1 protein, human
  • Interleukin-18
  • Interleukin-18 Receptor alpha Subunit
  • Receptors, Interleukin
  • Receptors, Interleukin-18
  • CD40 Ligand
  • Interleukin-12
  • Interferon-gamma