Cytokine release syndrome (CRS) embodies a mixture of clinical manifestations, including elevated circulating cytokine levels, acute systemic inflammatory symptoms and secondary organ dysfunction, which was first described in the context of acute graft-versus-host disease after allogeneic hematopoietic stem-cell transplantation and was later observed in pandemics of influenza, SARS-CoV and COVID-19, immunotherapy of tumor, after chimeric antigen receptor T (CAR-T) therapy, and in monogenic disorders and autoimmune diseases. Particularly, severe CRS is a very significant and life-threatening complication, which is clinically characterized by persistent high fever, hyperinflammation, and severe organ dysfunction. However, CRS is a double-edged sword, which may be both helpful in controlling tumors/viruses/infections and harmful to the host. Although a high incidence and high levels of cytokines are features of CRS, the detailed kinetics and specific mechanisms of CRS in human diseases and intervention therapy remain unclear. In the present review, we have summarized the most recent advances related to the clinical features and management of CRS as well as cutting-edge technologies to elucidate the mechanisms of CRS. Considering that CRS is the major adverse event in human diseases and intervention therapy, our review delineates the characteristics, kinetics, signaling pathways, and potential mechanisms of CRS, which shows its clinical relevance for achieving both favorable efficacy and low toxicity.

细胞因子释放综合征 (CRS) 体现了多种临床表现，包括循环细胞因子水平升高、急性全身炎症症状和继发器官功能障碍，这在异基因造血干细胞移植后急性移植物抗宿主病的背景下首次被描述后来在流感大流行、SARS-CoV 和 COVID-19、肿瘤免疫治疗、嵌合抗原受体 T (CAR-T) 治疗后以及单基因疾病和自身免疫性疾病中观察到。特别是严重的CRS是一种非常严重且危及生命的并发症，其临床特征为持续高热、过度炎症和严重的器官功能障碍。然而，CRS是一把双刃剑，可能既有助于控制肿瘤/病毒/感染，又可能对宿主有害。虽然高发病率和高水平的细胞因子是CRS的特征，但CRS在人类疾病和干预治疗中的详细动力学和具体机制仍不清楚。在本综述中，我们总结了与 CRS 的临床特征和管理相关的最新进展，以及阐明 CRS 机制的前沿技术。考虑到 CRS 是人类疾病和干预治疗中的主要不良事件，我们的综述描述了 CRS 的特征、动力学、信号通路和潜在机制，这表明其与实现良好疗效和低毒性的临床相关性。在本综述中，我们总结了与 CRS 的临床特征和管理相关的最新进展，以及阐明 CRS 机制的前沿技术。考虑到 CRS 是人类疾病和干预治疗中的主要不良事件，我们的综述描述了 CRS 的特征、动力学、信号通路和潜在机制，这表明其与实现良好疗效和低毒性的临床相关性。在本综述中，我们总结了与 CRS 的临床特征和管理相关的最新进展，以及阐明 CRS 机制的前沿技术。考虑到 CRS 是人类疾病和干预治疗中的主要不良事件，我们的综述描述了 CRS 的特征、动力学、信号通路和潜在机制，这表明其与实现良好疗效和低毒性的临床相关性。