Translating IL-6 biology into effective treatments
Translating IL-6 biology into effective treatments
复制标题
DOI：
10.1038/s41584-020-0419-z
复制
发表时间：
2020-04-23
影响因子：
33.7
通讯作者：
Kishimoto, Tadamitsu
中科院分区：
文献类型：
--
作者：
Choy, Ernest H.;De Benedetti, Fabrizio;Kishimoto, Tadamitsu
1973年，IL-6被鉴定为由T细胞分泌的可溶性因子，并且对于B细胞的抗体产生是重要的。自40多年前发现以来，IL-6通路已成为参与健康免疫调节和许多疾病调节异常的关键通路。IL-6通路的靶向已经导致用于各种风湿性疾病的创新治疗方法，例如类风湿性关节炎、幼年特发性关节炎、成人发病的斯蒂尔病、巨细胞动脉炎和大动脉炎，以及其他病症例如Castleman病和细胞因子释放综合征。靶向这一途径还确定了可能扩展到其他几种适应症的途径，如葡萄膜炎、视神经肌病和最近的COVID-19肺炎。为了纪念全球抗IL-6受体治疗十周年，我们讨论了IL-6生物学研究的历史和靶向IL-6信号传导的疗法的发展，包括成功和挑战，并强调风湿性疾病。作者叙述了IL-6生物学转化研究的最早阶段和治疗性IL-6的随后发展，6途径抑制剂，用于治疗自身免疫性风湿性疾病和潜在的许多其他适应症。
In 1973, IL-6 was identified as a soluble factor that is secreted by T cells and is important for antibody production by B cells. Since its discovery more than 40 years ago, the IL-6 pathway has emerged as a pivotal pathway involved in immune regulation in health and dysregulation in many diseases. Targeting of the IL-6 pathway has led to innovative therapeutic approaches for various rheumatic diseases, such as rheumatoid arthritis, juvenile idiopathic arthritis, adult-onset Still's disease, giant cell arteritis and Takayasu arteritis, as well as other conditions such as Castleman disease and cytokine release syndrome. Targeting this pathway has also identified avenues for potential expansion into several other indications, such as uveitis, neuromyelitis optica and, most recently, COVID-19 pneumonia. To mark the tenth anniversary of anti-IL-6 receptor therapy worldwide, we discuss the history of research into IL-6 biology and the development of therapies that target IL-6 signalling, including the successes and challenges and with an emphasis on rheumatic diseases.In this Perspective article, the authors recount the earliest stages of translational research into IL-6 biology and the subsequent development of therapeutic IL-6 pathway inhibitors for the treatment of autoimmune rheumatic diseases and potentially numerous other indications.