Ketamine suppresses endotoxin-induced NF-kappaB activation and cytokines production in the intestine.
BACKGROUND
Ketamine has been advocated for anesthesia in endotoxemic and other severely ill patients because it is a cardiovascular stimulant. However, ketamine also suppresses serum levels of endotoxin-induced tumor necrosis factor-alpha, and reduces mortality in mice in endotoxin shock. Our study was designed to investigate the protective effect of ketamine on the endotoxin-induced proinflammatory cytokines and nuclear factor kappa B (NF-kappaB) activation in vivo.


METHODS
Adult male Wistar rats were randomly divided into six groups: saline controls; rats challenged with endotoxin (5 mg kg(-1)) and treated with saline; challenged with endotoxin (5 mg kg(-1)) and treated with ketamine (0.5 mg kg(-1)); challenged with endotoxin (5 mg kg(-1)) and treated with ketamine (5 mg kg(-1)); challenged with endotoxin (5 mg kg(-1)) and treated with ketamine (50 mg kg(-1)); and saline injected and treated with ketamine (50 mg kg(-1)). TNF-alpha, IL-6 and NF-kappaB were investigated in the tissues of the intestine (jejunum) after 1, 4 and 6 h.


RESULTS
Endotoxin caused transient production of TNF-alpha and IL-6 and activation of NF-kappaB in the intestine at peak times of 1, 4 and 1 h, respectively. Ketamine 0.5 mg kg(-1) suppressed endotoxin-induced TNF-alpha elevation and inhibited NF-kappaB activation in the intestine; a dose of 5 mg kg(-1) was required to inhibit IL-6.


CONCLUSIONS
Ketamine suppresses the production of proinflammatory cytokines such as TNF-alpha and IL-6 in the intestine, possibly via inhibition of NF-kappaB.
Department of Anesthesiology, Jinling Hospital, College of Medicine, Nanjing University, Nanjing, China. jitazi0100@sina.com
J
J
Sun
X D
XD
Wang
H
H
Liu
J G
JG
Xu
D000778:Anesthetics, Dissociative / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000494:pharmacology; D004926:Escherichia coli; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors; D007583:Jejunum / Q000187:drug effects*; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D020011:Protective Agents / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D000093242:Interleukin-6 Inhibitors
D000778:Anesthetics, Dissociative; D004731:Endotoxins; D018691:Excitatory Amino Acid Antagonists; D018836:Inflammation Mediators; D007649:Ketamine; D016328:NF-kappa B; D020011:Protective Agents; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors