Differential response to treatment of relapsing–remitting multiple sclerosis with IFN-β: is there a dichotomy into T-helper-1 and -17 driven disease?

Abstract

Evaluation of: Axtell RC, de Jong BA, Boniface K et al.: T helper type 1 and type 17 cells determine efficacy of interferon-β in multiple sclerosis and experimental encephalomyelitis. Nat. Med. 16, 406–412 (2010). This study aimed to assess the mechanism of action of IFN-β in the treatment of relapsing–remitting multiple sclerosis (MS). It shows that IFN-β leads to amelioration of experimental autoimmune encephalomyelitis, the animal model of MS, if disease is induced with T-helper (Th)1 cells. In this case, response to therapy requires the presence of IFN-γ, and IL-10-secreting cells are induced. By contrast, in experimental autoimmune encephalomyelitis induced with Th17 cells, treatment with IFN-β leads to an aggravation of the condition. Patients with relapsing–remitting MS were subsequently stratified into responder (n = 12) and nonresponders (n = 14) to IFN-β treatment. In nonresponder patients, high pretreatment levels of IL-17F and endogenous IFN-β were present. These findings lead to the conclusion that there might be a dichotomy of disease biology of relapsing–remitting MS: MS patients with a Th1-biased disease respond to IFN-β, while patients with a Th17-biased disease do not. The study contains a number of interesting observations; however, further studies with larger numbers of patients are necessary to evaluate and possibly confirm the findings.