Details

Autor(en) / Beteiligte

• Steinman, Lawrence
• Raman, Chander
• 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

Titel

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

Ist Teil von

• Nature medicine, 2010-04, Vol.16 (4), p.406-412

Ort / Verlag

New York: Nature Publishing Group US

Erscheinungsjahr

2010

Quelle

MEDLINE

Beschreibungen/Notizen

• Interferon-β (IFN-β) is a mainstay therapy for multiple sclerosis. However, only two thirds of patients respond to therapy, and clinical symptoms worsen in some patients. Chandar Raman and his colleagues show that IFN-β alleviates disease induced by T helper type 1 cells and exacerbates disease induced by T helper type 17 cells in mice. They also show that these effects of IFN-β rely on IFN-γ signaling ( pages 376–377 ). Interferon-β (IFN-β) 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-β in experimental autoimmune encephalomyelitis (EAE) and relapsing-remitting multiple sclerosis (RRMS). IFN-β 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-β treatment still reduced IL-17 production without benefit. Both inhibition of IL-17 and induction of IL-10 depended on IFN-γ. In the absence of IFN-γ signaling, IFN-β therapy was ineffective in EAE. In RRMS patients, IFN-β 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-β 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-β.