TNF and TNF-receptors: From mediators of cell death and inflammation to therapeutic giants – past, present and future

摘要: Tumor Necrosis Factor (TNF), initially known for its tumor cytotoxicity, is a potent mediator of inflammation, as well many normal physiological functions in homeostasis and health, anti-microbial immunity. It also appears to have central role neurobiology, although this area TNF biology only recently emerging. Here, we review the basic effector functions, discuss advantages disadvantages therapeutic neutralization - now commonplace practice treatment wide range human inflammatory diseases. With over ten years experience, an emerging anti-TNF biologics available, their modes action, which appear be far more complex than had originally been anticipated. Finally, highlight current challenges intervention TNF: (i) discover produce orally delivered small molecule TNF-inhibitors, (ii) specifically target selected producing cells or individual (diseased) tissue targets, (iii) pre-identify responders. Although future looks bright, modulation moves into era personalized medicine with society's challenging expectations durable success achieving long-term disease remission.