More MS news articles for April 2002

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
Karni A, Koldzic DN, Bharanidharan P, Khoury SJ, Weiner HL.
Center for Neurologic Diseases and the Multiple Sclerosis Center, Brigham and Women's and Massachusetts General Hospitals, Harvard Medical School, 77 Avenue Louis Pasteur, 02115, Boston, MA, USA

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.