Interleukin-6 (IL-6) is a pivotal cytokine with a diverse repertoire of physiological functions that include regulation of immune cell proliferation and differentiation. Dysregulation of IL-6 signalling is associated with inflammatory and lymphoproliferative disorders such as rheumatoid arthritis and Castleman disease, and several classes of therapeutics have been developed that target components of the IL-6 signalling pathway. So far, monoclonal antibodies against IL-6 or IL-6 receptor (IL-6R) and Janus kinases (JAK) inhibitors have been successfully developed for the treatment of autoimmune diseases such as rheumatoid arthritis. However, clinical trials of agents targeting IL-6 signalling have also raised questions about the diseases and patient populations for which such agents have an appropriate benefit–risk profile. Knowledge from clinical trials and advances in our understanding of the complexities of IL-6 signalling, including the potential to target an IL-6 trans-signalling pathway, are now indicating novel opportunities for therapeutic intervention. In this Review, we overview the roles of IL-6 in health and disease and analyse progress with several approaches of inhibiting IL-6-signalling, with the aim of illuminating when and how to apply IL-6 blockade.

白细胞介素6（IL-6）是一种关键的细胞因子，具有多种生理功能，包括调节免疫细胞的增殖和分化。IL-6信号转导的失调与炎性和淋巴增生性疾病如类风湿性关节炎和Castleman病有关，并且已经开发出针对IL-6信号转导途径的成分的几种疗法。迄今为止，已成功开发出针对IL-6或IL-6受体（IL-6R）和Janus激酶（JAK）抑制剂的单克隆抗体，用于治疗自身免疫性疾病，例如类风湿性关节炎。但是，针对IL-6信号转导的药物的临床试验也引发了有关此类药物具有适当获益风险风险的疾病和患者人群的问题。反信号通路，现在表明治疗干预的新机会。在本综述中，我们概述了IL-6在健康和疾病中的作用，并分析了几种抑制IL-6信号传导的方法的进展，目的是阐明何时以及如何应用IL-6阻断作用。