Aggarwal Bharat B
Cytokine Research Section, Department of Bioimmunotherapy, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Box 143, Houston, Texas, USA.
Nat Rev Immunol. 2003 Sep;3(9):745-56. doi: 10.1038/nri1184.
Two different tumour-necrosis factors (TNFs), first isolated in 1984, were found to be cytotoxic to tumour cells and to induce tumour regression in mice. Research during the past two decades has shown the existence of a superfamily of TNF proteins consisting of 19 members that signal through 29 receptors. These ligands, while regulating normal functions such as immune responses, haematopoiesis and morphogenesis, have also been implicated in tumorigenesis, transplant rejection, septic shock, viral replication, bone resorption, rheumatoid arthritis and diabetes; so indicating their role as 'double-edged swords'. These cytokines either induce cellular proliferation, survival, differentiation or apoptosis. Blockers of TNF have been approved for human use in treating TNF-linked autoimmune diseases in the United States and other countries.
1984年首次分离出的两种不同的肿瘤坏死因子（TNFs）被发现对肿瘤细胞具有细胞毒性，并能诱导小鼠肿瘤消退。过去二十年的研究表明，存在一个由19个成员组成的TNF蛋白超家族，它们通过29种受体发出信号。这些配体在调节免疫反应、造血和形态发生等正常功能的同时，也与肿瘤发生、移植排斥、脓毒性休克、病毒复制、骨吸收、类风湿性关节炎和糖尿病有关；因此表明它们起着“双刃剑”的作用。这些细胞因子要么诱导细胞增殖、存活、分化，要么诱导细胞凋亡。在美国和其他国家，TNF阻滞剂已被批准用于治疗与TNF相关的自身免疫性疾病。
