Tseng Wen-Yi, Huang Yi-Shu, Lin Hsi-Hsien, Luo Shue-Fen, McCann Fiona, McNamee Kay, Clanchy Felix, Williams Richard
Kennedy Institute of Rheumatology, University of Oxford, OX3 7FY Oxford, UK; Division of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital-Keelung, Keelung, Taiwan.
Kennedy Institute of Rheumatology, University of Oxford, OX3 7FY Oxford, UK.
Cytokine. 2018 Jan;101:19-25. doi: 10.1016/j.cyto.2016.08.027. Epub 2016 Oct 26.
Tumour necrosis factor-α (TNF-α) is a highly pleiotropic cytokine with effects on multiple pathological and physiological functions via two distinct receptors, TNFR1 and TNFR2. Much of the pro- inflammatory action of TNF-α is mediated by TNFR1 whereas TNFR2 is thought to play an immunoregulatory and tissue protective role. Anti-TNF- α biologics have been extremely successful in treating a number of immune mediated pathologies, including rheumatoid arthritis, ankylosing spondylitis, psoriasis, psoriatic arthritis and inflammatory bowel disease. However, anti-TNF therapy has been shown to induce systemic lupus erythematosus and psoriasis in some patients, and to be deleterious in multiple sclerosis. It is hypothesized that these paradoxical effects of anti-TNF-α are due to inhibition of TNFR2 signalling. In this review, we will focus on the biology and pathophysiologic role of TNF-α and on the therapeutic implications of targeting TNF-α receptor signalling.
肿瘤坏死因子-α（TNF-α）是一种具有高度多效性的细胞因子，可通过两种不同的受体TNFR1和TNFR2对多种病理和生理功能产生影响。TNF-α的许多促炎作用是由TNFR1介导的，而TNFR2则被认为发挥免疫调节和组织保护作用。抗TNF-α生物制剂在治疗多种免疫介导的疾病方面极其成功，包括类风湿性关节炎、强直性脊柱炎、银屑病、银屑病关节炎和炎症性肠病。然而，抗TNF治疗已被证明在一些患者中会诱发系统性红斑狼疮和银屑病，并且对多发性硬化症有害。据推测，抗TNF-α的这些矛盾效应是由于TNFR2信号传导受到抑制。在本综述中，我们将重点关注TNF-α的生物学和病理生理作用以及靶向TNF-α受体信号传导的治疗意义。
