细胞因子是分泌的信号蛋白，发挥着免疫反应的启动、维持和解决中的关键作用。虽然细胞因子独特的控制免疫功能的能力引起了在癌症、自身免疫和传染病的临床兴趣，但细胞因子治疗的使用仍受限制。这部分是由于细胞因子能够作用于许多细胞类型并影响多种生物功能，导致剂量限制的毒性或缺乏功效。结合结构生物学、蛋白质工程和受体药理学的最新研究揭示了细胞因子受体激活机制的新见解，证明了细胞因子功能的许多方面是高度可调的。本文中，我们讨论了这些努力克服细胞因子多向性并增强这一重要类信号分子的治疗潜力的药理学原则。©2022 Springer Nature Limited.

Cytokines are secreted signalling proteins that play essential roles in the initiation, maintenance and resolution of immune responses. Although the unique ability of cytokines to control immune function has garnered clinical interest in the context of cancer, autoimmunity and infectious disease, the use of cytokine-based therapeutics has been limited. This is due, in part, to the ability of cytokines to act on many cell types and impact diverse biological functions, resulting in dose-limiting toxicity or lack of efficacy. Recent studies combining structural biology, protein engineering and receptor pharmacology have unlocked new insights into the mechanisms of cytokine receptor activation, demonstrating that many aspects of cytokine function are highly tunable. Here, we discuss the pharmacological principles underlying these efforts to overcome cytokine pleiotropy and enhance the therapeutic potential of this important class of signalling molecules.© 2022. Springer Nature Limited.