Laboratory of Molecular Immunology and the Immunology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1674, USA; email:
Annu Rev Immunol. 2019 Apr 26;37:295-324. doi: 10.1146/annurev-immunol-042718-041447. Epub 2019 Jan 16.
Cytokines are secreted or otherwise released polypeptide factors that exert autocrine and/or paracrine actions, with most cytokines acting in the immune and/or hematopoietic system. They are typically pleiotropic, controlling development, cell growth, survival, and/or differentiation. Correspondingly, cytokines are clinically important, and augmenting or attenuating cytokine signals can have deleterious or therapeutic effects. Besides physiological fine-tuning of cytokine signals, altering the nature or potency of the signal can be important in pathophysiological responses and can also provide novel therapeutic approaches. Here, we give an overview of cytokines, their signaling and actions, and the physiological mechanisms and pharmacologic strategies to fine-tune their actions. In particular, the differential utilization of STAT proteins by a single cytokine or by different cytokines and STAT dimerization versus tetramerization are physiological mechanisms of fine-tuning, whereas anticytokine and anticytokine receptor antibodies and cytokines with altered activities, including cytokine superagonists, partial agonists, and antagonists, represent new ways of fine-tuning cytokine signals.
细胞因子是分泌或其他方式释放的多肽因子，发挥自分泌和/或旁分泌作用，大多数细胞因子在免疫和/或造血系统中发挥作用。它们通常具有多效性，控制着发育、细胞生长、存活和/或分化。相应地，细胞因子具有重要的临床意义，增强或减弱细胞因子信号可能产生有害或治疗效果。除了细胞因子信号的生理微调外，改变信号的性质或效力在病理生理反应中也很重要，并且还可以提供新的治疗方法。在这里，我们概述了细胞因子及其信号转导和作用，以及生理机制和药理学策略来微调它们的作用。特别是，单个细胞因子或不同细胞因子对 STAT 蛋白的不同利用以及 STAT 二聚体与四聚体化是微调的生理机制，而抗细胞因子和抗细胞因子受体抗体以及具有改变活性的细胞因子，包括细胞因子超激动剂、部分激动剂和拮抗剂，则代表了微调细胞因子信号的新方法。
