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  • Title: Ketamine suppresses endotoxin-induced NF-kappaB activation and cytokines production in the intestine.
    Author: Sun J, Wang XD, Liu H, Xu JG.
    Journal: Acta Anaesthesiol Scand; 2004 Mar; 48(3):317-21. PubMed ID: 14982564.
    Abstract:
    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. CONCLUSION: Ketamine suppresses the production of proinflammatory cytokines such as TNF-alpha and IL-6 in the intestine, possibly via inhibition of NF-kappaB.
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