Interleukin-6 (IL-6) plays a crucial role in host defense against infection and tissue injuries and is a bioindicator of multiple distinct types of cytokine storms. In this review, we present the current understanding of the diverse roles of IL-6, its receptors, and its signaling during acute severe systemic inflammation. IL-6 directly affects vascular endothelial cells, which produce several types of cytokines and chemokines and activate the coagulation cascade. Endothelial cell dysregulation, characterized by abnormal coagulation and vascular leakage, is a common complication in cytokine storms. Emerging evidence indicates that a humanized anti-IL-6 receptor antibody, tocilizumab, can effectively block IL-6 signaling and has beneficial effects in rheumatoid arthritis, juvenile systemic idiopathic arthritis, and Castleman’s disease. Recent work has also demonstrated the beneficial effect of tocilizumab in chimeric antigen receptor T-cell therapy-induced cytokine storms as well as coronavirus disease 2019 (COVID-19). Here, we highlight the distinct contributions of IL-6 signaling to the pathogenesis of several types of cytokine storms and discuss potential therapeutic strategies for the management of cytokine storms, including those associated with sepsis and COVID-19.

白介素 6 (IL-6) 在宿主防御感染和组织损伤中发挥着至关重要的作用，并且是多种不同类型细胞因子风暴的生物指示剂。在这篇综述中，我们介绍了目前对 IL-6、其受体及其信号在急性严重全身炎症过程中的不同作用的理解。IL-6 直接影响血管内皮细胞，血管内皮细胞产生多种类型的细胞因子和趋化因子并激活凝血级联反应。内皮细胞失调，以异常凝血和血管渗漏为特征，是细胞因子风暴的常见并发症。新的证据表明，人源化抗 IL-6 受体抗体托珠单抗 (tocilizumab) 可以有效阻断 IL-6 信号传导，并对类风湿性关节炎、青少年系统性特发性关节炎和 Castleman 病具有有益作用。最近的工作还证明了托珠单抗在嵌合抗原受体 T 细胞疗法诱导的细胞因子风暴以及 2019 年冠状病毒病 (COVID-19) 中具有有益作用。在这里，我们强调 IL-6 信号传导对几种类型细胞因子风暴发病机制的独特贡献，并讨论管理细胞因子风暴的潜在治疗策略，包括与脓毒症和 COVID-19 相关的策略。