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IL-17 和成功的局限性。

IL-17 and limits of success.

机构信息

Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States.

Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States.

出版信息

Cell Immunol. 2019 May;339:33-40. doi: 10.1016/j.cellimm.2018.09.001. Epub 2018 Sep 17.

Abstract

Interleukin-17 (IL-17) is a potent proinflammatory cytokine that protects a host against fungal and extracellular bacterial infections. On the other hand, excessive or dysregulated production of IL-17 underlines susceptibility to autoimmune disease. Consequently, blocking IL-17 has become an effective strategy for modulating several autoimmune diseases, including multiple sclerosis (MS), psoriasis, and rheumatoid arthritis (RA). Notably, however, IL-17 blockade remains ineffective or even pathogenic against important autoimmune diseases such as inflammatory bowel disease (IBD). Furthermore, the efficacy of IL-17 blockade against other autoimmune diseases, including type 1 diabetes (T1D) is currently unknown and waiting results of ongoing clinical trials. Coming years will determine whether the efficacy of IL-17 blockade is limited to certain autoimmune diseases or can be expanded to other autoimmune diseases. These efforts include new clinical trials aimed at testing second-generation agents with the goal of increasing the efficiency, spectrum, and ameliorating side effects of IL-17 blockade. Here we briefly review the roles of IL-17 in the pathogenesis of selected autoimmune diseases and provide updates on ongoing and recently completed trials of IL-17 based immunotherapies.

摘要

白细胞介素-17(IL-17)是一种有效的促炎细胞因子,可保护宿主免受真菌和细胞外细菌感染。另一方面,IL-17 的过度或失调产生是自身免疫性疾病易感性的基础。因此,阻断 IL-17 已成为调节多种自身免疫性疾病的有效策略,包括多发性硬化症(MS)、银屑病和类风湿关节炎(RA)。然而,值得注意的是,IL-17 阻断在某些重要的自身免疫性疾病(如炎症性肠病(IBD))中仍然无效甚至致病。此外,IL-17 阻断对其他自身免疫性疾病(包括 1 型糖尿病(T1D))的疗效目前尚不清楚,正在等待正在进行的临床试验结果。未来几年将决定 IL-17 阻断的疗效是否仅限于某些自身免疫性疾病,还是可以扩展到其他自身免疫性疾病。这些努力包括旨在测试第二代药物的新临床试验,以期提高 IL-17 阻断的效率、谱并改善其副作用。本文简要综述了 IL-17 在几种自身免疫性疾病发病机制中的作用,并提供了基于 IL-17 的免疫疗法的正在进行和最近完成的试验的最新情况。

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