Ketamine suppresses intestinal NF-kappa B activation and proinflammatory cytokine in endotoxic rats.
OBJECTIVE
To investigate the protective effect of ketamine on the endotoxin-induced proinflammatory cytokines and NF-kappa B activation in the intestine.


METHODS
Adult male Wistar rats were randomly divided into 6 groups: (a) normal saline control, (b) challenged with endotoxin (5 mg/kg) and treated by saline, (c) challenged with endotoxin (5 mg/kg) and treated by ketamine (0.5 mg/kg), (d) challenged with endotoxin (5 mg/kg) and treated by ketamine (5 mg/kg ), (e) challenged with endotoxin (5 mg/kg) and treated by ketamine (50 mg/kg), and (f) saline injected and treated by ketamine (50 mg/kg). After 1, 4 or 6 h, TNF-alpha and IL-6 mRNA were investigated in the tissues of the intestine (jejunum) by RT-PCR. TNF-alpha and IL-6 were measured by ELISA. We used electrophoretic mobility shift assay (EMSA) to investigate NF-kappa B activity in the intestine.


RESULTS
NF-kappa B activity, the expression of TNF-alpha and IL-6 were enhanced in the intestine by endotoxin. Ketamine at a dose of 0.5 mg/kg could suppress endotoxin-induced TNF-alpha mRNA and protein elevation and inhibit NF-kappa B activation in the intestine. However the least dosage of ketamine to inhibit IL-6 was 5 mg/kg in our experiment.


CONCLUSIONS
Ketamine can suppress endotoxin-induced production of proinflammatory cytokines such as TNF-alpha and IL-6 production in the intestine. This suppressive effect may act through inhibiting NF-kappa B.
Sun
Jie
J
Department of Anesthesiology, Nanjing University College of Medicine, Jinling Hospital, 305 East Zhongshan Road, Nanjing 210002, Jiangsu Province, China. dgsunjie@hotmail.com
Wang
Xiao-Dong
XD
Liu
Hong
H
Xu
Jian-Guo
JG
D000778:Anesthetics, Dissociative / Q000494:pharmacology*; D000818:Animals; D019446:Endotoxemia / Q000378:metabolism*; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors; D007413:Intestinal Mucosa / Q000378:metabolism*; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D000093242:Interleukin-6 Inhibitors
D000778:Anesthetics, Dissociative; D018836:Inflammation Mediators; D007649:Ketamine; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors