Effect of ketamine on NF-kappa B activity and TNF-alpha production in endotoxin-treated rats

Abstract

The effects of ketamine on endotoxin-induced NF-kappaB activation and TNF-alpha expression were studied in vivo. A sepsis model was created by bolus injection of endotoxin (5 mg/kg) into the tail vein of adult Wistar rats. The rats were immediately treated with various doses of ketamine (0.5, 5, or 50 mg/kg) or 0.9% NaCl (10 ml/kg) i.p. At 1, 4, or 6 hr post-treatment, NF-kappaB and TNF-alpha were assayed in the intestine, liver, and lung by electrophoretic mobility shift assay (EMSA) and reverse-transcription polymerase chain reaction (RT-PCR), respectively. Serum TNF-alpha was analyzed by ELISA. Endotoxin enhanced NF-kappaB activity and TNF-alpha expression in the intestine, liver, and lung and it increased TNF-alpha concentration in serum. Ketamine dosages 0.5 mg/kg suppressed the endotoxin-induced NF-kappaB activation and TNF-alpha expression in the intestine. The lowest dose to inhibit NF-kappaB activity and TNF-alpha expression in the lung was 5 mg/kg. Ketamine did not inhibit endotoxin-induced NF-kappaB activity or TNF-alpha expression in the liver; ketamine itself at a dose of 50 mg/kg enhanced NF-kappaB activity and TNF-alpha expression in the liver. Ketamine dosage 0.5 mg/kg inhibited endotoxin-induced TNF-alpha elevation in the serum. In conclusion, ketamine can suppress the induction of NF-kappaB and TNF-alpha by endotoxin in vivo. Subanesthetic dosages of ketamine have an anti-inflammatory effect, but large dosages may be harmful.