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- Title
T helper type 1 and 17 cells determine efficacy of interferon-beta in multiple sclerosis and experimental encephalomyelitis.
- Authors
Axtell, Robert C; de Jong, Brigit A; Boniface, Katia; van der Voort, Laura F; Bhat, Roopa; De Sarno, Patrizia; Naves, Rodrigo; Han, May; Zhong, Franklin; Castellanos, Jim G; Mair, Robert; Christakos, Athena; Kolkowitz, Ilan; Katz, Liat; Killestein, Joep; Polman, Chris H; de Waal Malefyt, René; Steinman, Lawrence; Raman, Chander
- Abstract
Interferon-beta (IFN-beta) is the major treatment for multiple sclerosis. However, this treatment is not always effective. Here we have found congruence in outcome between responses to IFN-beta in experimental autoimmune encephalomyelitis (EAE) and relapsing-remitting multiple sclerosis (RRMS). IFN-beta was effective in reducing EAE symptoms induced by T helper type 1 (T(H)1) cells but exacerbated disease induced by T(H)17 cells. Effective treatment in T(H)1-induced EAE correlated with increased interleukin-10 (IL-10) production by splenocytes. In T(H)17-induced disease, the amount of IL-10 was unaltered by treatment, although, unexpectedly, IFN-beta treatment still reduced IL-17 production without benefit. Both inhibition of IL-17 and induction of IL-10 depended on IFN-gamma. In the absence of IFN-gamma signaling, IFN-beta therapy was ineffective in EAE. In RRMS patients, IFN-beta nonresponders had higher IL-17F concentrations in serum compared to responders. Nonresponders had worse disease with more steroid usage and more relapses than did responders. Hence, IFN-beta is proinflammatory in T(H)17-induced EAE. Moreover, a high IL-17F concentration in the serum of people with RRMS is associated with nonresponsiveness to therapy with IFN-beta.
- Publication
Nature medicine, 2010, Vol 16, Issue 4, p406
- ISSN
1546-170X
- Publication type
Journal Article
- DOI
10.1038/nm.2110