TUMOR-NECROSIS-FACTOR-ALPHA UP-REGULATES HUMAN MICROGLIAL CELL PRODUCTION OF INTERLEUKIN-10 IN-VITRO

Interleukin (IL)-10 appears to play an important regulatory role in th e systemic inflammatory response; however, production of IL-10 within the human central nervous system has not been described, Using culture s of human fetal microglial cells, the resident macrophages of the bra in, we investigated the production and regulation of bioactive IL-10. Lipopolysaccharide stimulated acute release of tumor necrosis factor ( TNF)-alpha (peak by 8 h) and delayed production of IL-10 (over a 48-h period) in microglial cell cultures, Treatment of microglial cell cult ures with TNF-alpha and IL-6 resulted in a dose-dependent release of I L-10. These cytokines also induced expression of IL-10 mRNA. Treatment of microglial cell cultures with IL-10 markedly inhibited TNF-alpha a nd IL-6 production, These findings suggest that during inflammation wi thin the brain, acute release of TNF-alpha and IL-6 by activated micro glia could promote subsequent release of IL-10, which functions to min imize the potential neurotoxic effects of proinflammatory cytokines.