Ketamine Inhibits Calcium Elevation and Hydroxyl Radical and Nitric Oxide Production in Lipopolysaccharide-Stimulated NR8383 Alveolar Macrophages

Macrophages play a critical role in mediating inflammatory processes; activated macrophages respond to endotoxin by releasing pro-inflammatory cytokines including tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and IL-6. Ketamine, a widely used anesthetic agent, has unequivocally anti-inflammatory effects in vivo and in vitro. However, the detailed mechanisms for the anti-inflammatory effects of ketamine in microglia have not been elucidated yet. This study aimed to evaluate the effects of ketamine on lipopolysaccharide (LPS)-induced nitric oxide (NO), hydroxyl radical (center dot OH) production, and intracellular calcium accumulation in macrophages. Macrophages were pretreated with ketamine at the concentrations of 10, 100, and 1,000 mu M 1 h before LPS stimulation. The production of NO and center dot OH in the culture supernatant of macrophages was assayed by Griess Reagent Kit. LPS enhanced NO and center dot OH production and provoked a significant intracellular calcium elevation. With the concentrations higher than 100 mu M, ketamine inhibited LPS-induced NO and center dot OH accumulation and intracellular calcium elevation. However, a low concentration of ketamine (10 mu M) did not exert anti-inflammatory effects. These results suggest that intracellular calcium elevation is, at least, partially involved in the inhibitory effect of ketamine.