肿瘤坏死因子α及其抑制剂的研究进展

Research progress on tumor necrosis factor α and its inhibitors

肿瘤坏死因子(TNF)α是一种在多种生物效应中起作用的细胞因子,主要由单核细胞、巨噬细胞和胸腺依赖淋巴细胞产生,分为溶解型和膜结合型。TNFα通过与其受体(TNFR)特异性结合引起一系列细胞因子改变,进而实现促细胞生长和程序性细胞死亡并促进牙周炎、种植体周围炎以及局限性肠炎和类风湿性关节炎等疾病发展的作用。TNFα抑制剂分为大分子抑制剂和活性小分子抑制剂,种类繁多,作用机制复杂,已大量应用于临床治疗并取得了优异的疗效;而新型TNFα抑制剂TNFR1前配体结合序列复合物对于TNFα引起的程序性细胞死亡、关节炎破骨活动有明显的抑制作用,具有治疗TNFα参与的炎性疾病的潜能。

Tumor necrosis factor（TNF）α is a cytokine involved in various biological processes. TNFα is mainly produced by monocytes, macrophages, and thymus-dependent lymphocytes. TNFα can be classified into two groups, namely, the soluble type and membrane type. TNFα can cause a series of cytokine changes via binding to its receptor TNFR, there by resulting in accelerated cell growth or programmed death. It can promote the development of periodontitis, peri-implantitis, segmental enteritis, and rheumatoid arthritis. TNFα inhibitors can be classified as either macromolecule type or small active molecule type. Various TNFα inhibitors exist and have complex mechanisms. TNFα inhibitors are widely used in clinical applications and demonstrate excellent effects. The pre-ligand binding assembly domain of TNFR1 is a new type of TNFα inhibitor tha thas great potential for the treatment of inflammatory diseases involving TNFα. Thus, TNFct-induced programmed cell death and joint osteoclast activity can be inhibited.