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.

细胞因子是分泌的信号蛋白，在免疫反应的启动、维持和解决中发挥重要作用。尽管细胞因子控制免疫功能的独特能力在癌症、自身免疫和传染病领域引起了临床兴趣，但基于细胞因子的治疗方法的使用受到限制。这在一定程度上是由于细胞因子能够作用于许多细胞类型并影响不同的生物功能，从而导致剂量限制性毒性或缺乏疗效。最近结合结构生物学、蛋白质工程和受体药理学的研究揭示了细胞因子受体激活机制的新见解，证明细胞因子功能的许多方面是高度可调的。这里，