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Effect of Ketamine on NF-kappa B Activity and TNF-alpha Production in Endotoxin-Treated Rats

Address correspondence Jianguo Xu M.D., Department of Anesthesiology, Jinling Hospital, 305 East Zhongshan Road, Nanjing 210002, People’s Republic of China; tel 86-25 480 6839; 86-25 8580 0906; e-mail dgsunjie{at}hotmail.com.

The effects of ketamine on endotoxin-induced NF-B activation and TNF- 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) ip. At 1, 4, or 6 hr post-treatment, NF-B and TNF- 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- was analyzed by ELISA. Endotoxin enhanced NF-B activity and TNF- expression in the intestine, liver, and lung and it increased TNF- concentration in serum. Ketamine dosages 0.5 mg/kg suppr essed the endotoxin-induced NF-B activation and TNF- expression in the intestine. The lowest dose to inhibit NF-B activity and TNF- expression in the lung was 5 mg/kg. Ketamine did not inhibit endotoxin-induced NF-B activity or TNF- expression in the liver; ketamine itself at a dose of 50 mg/kg enhanced NF-B activity and TNF- expression in the liver. Ketamine dosage 0.5 mg/kg inhibited endotoxin-induced TNF- elevation in the serum. In conclusion, ketamine can suppress the induction of NF-B and TNF- by endotoxin in vivo. Subanesthetic dosages of ketamine have an anti-inflammatory effect, but large dosages may be harmful.

Keywords: endotoxin, NF-B, ketamine, TNF-, sepsis

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