Molecular Immunology Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
J Clin Pharmacol. 2023 Dec;63(12):1330-1343. doi: 10.1002/jcph.2325. Epub 2023 Aug 9.
Janus kinase (JAK) inhibitors are a novel group of immunosuppressive drugs approved to treat certain rheumatic and allergic disorders; however, their efficacy in the regulation of alloimmune responses after solid organ transplantation has not yet been elucidated. In the present review, we have summarized the results of in vitro, in vivo, experimental, and clinical trial studies about the efficacy and safety of JAK inhibitors in improving allograft survival in solid organ transplantations, including kidney, heart, lung, and liver transplants. Moreover, reports on administering JAK inhibitors to steroid-resistant patients with graft versus host disease (GvHD) after solid organ transplantation have been reviewed. Overall findings are suggestive of a beneficial role for JAK inhibitors in organ transplantation: for example, they have been shown to improve allograft function, reduce the rate and score of acute rejection, downregulate the expression of proinflammatory cytokines and adhesion molecules, and decrease oxidative stress. However, the adverse effects of these drugs, in particular bone marrow suppression and infection, remain an obstacle.
Janus 激酶 (JAK) 抑制剂是一类新型免疫抑制剂,已被批准用于治疗某些风湿性和过敏性疾病;然而,它们在调节实体器官移植后同种免疫反应方面的疗效尚未阐明。在本综述中,我们总结了 JAK 抑制剂在改善实体器官移植中同种移植物存活方面的体外、体内、实验和临床试验研究的结果,包括肾、心、肺和肝移植。此外,还回顾了 JAK 抑制剂在实体器官移植后用于治疗类固醇耐药性移植物抗宿主病 (GvHD) 患者的报告。总体研究结果表明 JAK 抑制剂在器官移植中具有有益作用:例如,它们已被证明可改善移植物功能、降低急性排斥反应的发生率和评分、下调促炎细胞因子和黏附分子的表达、减少氧化应激。然而,这些药物的不良反应,特别是骨髓抑制和感染,仍然是一个障碍。