Cytokines are involved in intestinal homeostasis and pathological processes associated with inflammatory bowel disease (IBD). The biological effects of cytokines, including several involved in the pathology of Crohn’s disease and ulcerative colitis, occur as a result of receptor-mediated signalling through the Janus kinase (JAK) and signal transducer and activator of transcription (STAT) DNA-binding families of proteins. Although therapies targeting cytokines have revolutionized IBD therapy, they have historically targeted individual cytokines, and an unmet medical need exists for patients who do not respond to or lose response to these treatments. Several small-molecule inhibitors of JAKs that have the potential to affect multiple pro-inflammatory cytokine-dependent pathways are in clinical development for the treatment of IBD, with one agent, tofacitinib, already approved for ulcerative colitis and several other agents with demonstrated efficacy in early phase trials. This Review describes the current understanding of JAK–STAT signalling in intestinal homeostasis and disease and the rationale for targeting this pathway as a treatment for IBD. The available evidence for the efficacy, safety and pharmacokinetics of JAK inhibitors in IBD as well as the potential approaches to optimize treatment with these agents, such as localized delivery or combination therapy, are also discussed.

细胞因子参与与炎症性肠病（IBD）相关的肠道稳态和病理过程。细胞因子的生物学效应（包括几种参与克罗恩氏病和溃疡性结肠炎病理的因子）是通过Janus激酶（JAK）和信号转导子以及STAT的DNA结合激活子（STAT）介导的受体介导的信号产生的蛋白质。尽管针对细胞因子的疗法已经彻底改变了IBD治疗，但历史上它们针对的是单个细胞因子，对于那些对这些疗法无反应或失去反应的患者，医疗需求仍未得到满足。有几种可能会影响多种促炎细胞因子依赖性途径的JAK小分子抑制剂正在临床开发中，以一种药物治疗IBD，托法替尼，已经被批准用于溃疡性结肠炎和其他几种药物，在早期试验中显示出疗效。这篇综述描述了目前对肠道稳态和疾病中JAK-STAT信号转导的理解，以及针对这种途径作为IBD治疗的理由。还讨论了JAK抑制剂在IBD中的有效性，安全性和药代动力学的可用证据，以及优化这些药物治疗的潜在方法，例如局部递送或联合治疗。