Dexmedetomidine attenuates lipopolysaccharide-induced proinflammatory response in primary microglia.

ABSTRACT

BACKGROUND: Neuroinflammation mediated by microglia has been implicated in delirium. Suppression of microglial activation may therefore contribute to alleviate delirium. It has been reported that dexmedetomidine (DEX) has a potent anti-inflammatory property. In the present study, we investigated the effects of DEX on the production of proinflammatory mediators in lipopolysaccharide-stimulated microglia. MATERIALS AND METHODS: The concentrations of DEX were chosen to correspond to 1, 10, and 100 times of clinically relevant concentration (i.e., 1, 10, and 100ng/mL). The levels of proinflammatory mediators, such as inducible nitric oxide synthase or nitric oxide, prostaglandin E(2), interleukin 1ß, and tumor necrosis factor α, were measured. RESULTS: DEX at 1ng/mL did not affect the production of proinflammatory mediators. DEX at 10 and 100ng/mL significantly inhibited the release of nitric oxide, prostaglandin E(2), interleukin 1ß, and tumor necrosis factor α and the expression of inducible nitric oxide synthase messenger RNA. CONCLUSIONS: These results suggest that DEX is a potent suppressor of lipopolysaccharide-induced inflammation in activated microglia and may be a potential therapeutic agent for the treatment of intensive care unit delirium.