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T helper type 1 and 17 cells determine efficacy of interferon-beta in multiple sclerosis and experimental encephalomyelitis NATURE MEDICINE Axtell, R. C., de Jong, B. A., Boniface, K., Van der Voort, L. F., Bhat, R., De Sarno, P., Naves, R., Han, M., Zhong, F., Castellanos, J. G., Mair, R., Christakos, A., Kolkowitz, I., Katz, L., Killestein, J., Polman, C. H., Malefyt, R. d., Steinman, L., Raman, C. 2010; 16 (4): 406-U21

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.

View details for DOI 10.1038/nm.2110

View details for Web of Science ID 000276446800044

View details for PubMedID 20348925

View details for PubMedCentralID PMC3042885