T helper type 1 and 17 cells determine efficacy of interferon-beta in multiple sclerosis and experimental encephalomyelitis.
T helper type 1 and 17 cells determine efficacy of interferon-beta in multiple sclerosis and experimental encephalomyelitis.
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干扰素-β是多发性硬化症(MS)的主要治疗方法。然而，这种治疗并不总是有效的。在这里，我们看到在实验性自身免疫性脑脊髓炎(EAE)和复发-缓解型多发性硬化症(RRMS)中对干扰素-β的反应结果是一致的。干扰素-β能有效降低Th1细胞诱导的EAE，但加重Th1细胞诱导的疾病。TH1 EAE的有效治疗与脾组织中IL-10的升高有关。在Th17病中，IL-10的含量在治疗过程中没有改变，尽管出人意料的是，干扰素-β仍然降低了IL-17的水平，但没有带来任何好处。IL-17的抑制和IL-10的诱导均依赖于干扰素-γ。在缺乏干扰素-γ信号的情况下，干扰素-β治疗对EAE无效。在RRMS中，干扰素-β无应答者的血清IL-17F水平高于应答者。与有反应的人相比，无反应的人疾病更严重，类固醇的使用更多，复发更多。因此，干扰素-β在Th17诱导的EAE中具有促炎作用。此外，RRMS患者血清中高IL-17F水平与干扰素-β治疗无反应有关。
Interferon-β is the major treatment for multiple sclerosis (MS). However, this treatment is not always effective. Here we see congruence in outcome between responses to IFN-β in experimental autoimmune encephalomyelitis (EAE) and relapsing-remitting MS (RRMS). IFN-β is effective in reducing EAE induced by TH1 cells, but exacerbated disease induced by TH17. Effective treatment in TH1 EAE correlated with increased IL-10 in the spleen. In TH17 disease, the amount of IL-10 was unaltered by treatment, though unexpectedly IFN-β still reduced IL-17 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, IFN-β non-responders had higher IL-17F in serum compared to responders. Non-responders had worse disease with more steroid usage and more relapses than responders. Hence, IFN-β is pro-inflammatory in TH17 induced EAE. Moreover, high IL-17F in the serum of RRMS patients is associated with non-responsiveness to therapy with IFN-β.
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