T helper type 1 and 17 cells determine efficacy of interferon-beta in multiple sclerosis and experimental encephalomyelitis

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; et. al.

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.

Más información

Título según WOS: ID WOS:000276446800044 Not found in local WOS DB
Título de la Revista: NATURE MEDICINE
Volumen: 16
Número: 4
Editorial: NATURE PORTFOLIO
Fecha de publicación: 2010
Página de inicio: 406
Página final: U21
DOI:

10.1038/nm.2110

Notas: ISI