Autocrine activation of microglia by tumor necrosis factor-α

In the central nervous system (CNS), tumor necrosis factor-α (TNF-α) derived from activated microglia plays a critical role as an inflammatory mediator. In this study, we examined the function of TNF-α as an autocrine mediator in microglial activation. TNF-α induced TNF-α production by microglia through ligation of TNF receptor 1 (TNFR1). TNF-α also increased the production of other inflammatory mediators. The activation of microglia by lipopolysaccharide is partially mediated by microglia-derived TNF-α. These findings suggest the existence of a positive feedback loop in the activation of microglia via TNF-α. This autocrine loop may be involved in the prolonged activation of microglia.