IL-6/gp130在类风湿性关节炎疾病中的作用:从机制到临床转化进展

Role of IL-6/gp130 in rheumatoid arthritis:study progress from mechanism to clinical transformation

白细胞介素-6(IL-6)参与慢性炎症的发生、自身抗体的产生以及血管通透性改变等过程,是类风湿性关节炎发作期间最高表达的炎性介质之一,成为药物治疗的靶点。不同来源的白细胞介素-6可以通过与白细胞介素-6Rα和gp130结合,经经典信号转导或转移信号转导或聚类信号转导模式,介导JAK-STAT、ERK-MAPK和PI3K-AKT3种途径的细胞内信号转导,引起炎症发生。针对白细胞介素-6/gp130的靶向药物逐步被开发,但是仍然存在着诸多不良反应和副作用,靶向给药途径或局部给药途径治疗类风湿性关节炎被看好。本文总结了以白细胞介素-6及其受体为靶标的类风湿性关节炎治疗药物研发与使用情况,讨论了新型给药系统在类风湿性关节炎治疗研究中的优势,期望能为治疗类风湿性关节炎药物的研发提供新的思路。

Interleukin-6(IL-6) is involved in development of chronic inflammation,autoantibody production and vascular permeability changes.It is one of the most highly expressed inflammatory mediators during the onset of rheumatoid arthritis and has become a target for drug therapy.Different sources of IL-6 can mediate JAK- STAT,ERK-MAPK and PI3K-AKT through classic-signaling or trans- signaling or cluster-signaling transduction pathway by binding to IL-6Rα and gp130.Intracellular signal transduction causes inflammation.Targeted drugs against IL-6/gp130 have been gradually developed,but there are still many adverse reactions and side effects.Thus targeted drug delivery or local treatment of rheumatoid arthritis are favored.This article summarized the current development and application of drugs targeting IL-6 and its receptors in the treatment of rheumatoid arthritis,discussed the advantages of new drug delivery systems in the treatment of rheumatoid arthritis,expecting to provide new ideas for developing new drugs for treatment of rheumatoid arthritis.