Effects of ketamine on endotoxin-induced proinflammatory cytokine production and NF-?B activation in vivo / 中华麻醉学杂志

ABSTRACT

Objective To investigate the effects of ketamine on endotexin-induced production of proinflammatory cytokines(IL-6, TNF-?) and activation of their medulating factor NF-?B in vivo. Methods Forty adult male SD rats weighing 200-250 g were randomly divided into 4 groups (Ⅰ)control group(n=10); (Ⅱ) endotoxin group received intravenous endotoxin(Escherichia coli O111 B4, Sigma) 5 mg?kg~(-1)(n=10); (Ⅲ, Ⅳ)endotexin+ketamine group received ketamine or 5 or 10mg?kg~(-1)?h~(-1) after endotoxin(n=10). The animals were anesthetized with urethane i.p. (1g?kg~(-1)). Carotid artery was cannulated for BP and HR monitoring and jugular vein was cannulated for fluid or drug administration. Two hours after endotoxin administration the animals were sacrificed by exsanguination. Blood was collected and peripheral blood monocytes(PBMC) were isolated. NF-?B activity in PBMC was measured by EMSA and plasma TNF-? and IL-6 levels were determined by ELISA. Results Progressive hypotension and tachycardia developed after endotoxin administration. Endotexin also increased NF-?B activity in PBMCs and plasma TNF-? and IL-6. Ketamine 10 mg?kg~(-1) attenuated the endotexin-induced hemedynamie levels. Ketamine(5, 50 mg?kg~(-1)?h~(-1)) suppressed NF-?B activity in PBMC and inhihited plasma TNF-? level but plasma IL-6 level was not affected. Conclusion Ketamine can suppress endotoxin-induced NF-?appa B activation. Subanesthetic dose of ketamine has anti-inflammatory action.