Effects of Ketamine on Pulmonary Inflammatory Responses and Survival in Rats Exposed to Polymicrobial Sepsis
AbstractPURPOSE. Ketamine is reported to suppress production of proinflammatory cytokines and activity of nuclear factor-kappa B (NF-?B) after lipopolysaccharide (LPS) stimulation. Our study was designed to investigate the effects of ketamine on pulmonary inflammatory responses and survival in a clinically relevant model of polymicrobial sepsis, induced by cecal ligation and puncture (CLP). METHODS. After the induction of sepsis or sham-operation, animals were treated with ketamine (0.5, 5 or 10 mg/kg) or saline (10 ml/kg) at 3h after operation. At 6 h post-operation, the levels of tumor necrosis factor alpha (TNF-?) and interleukin (IL)-6, activity of NF-?B, expression of Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4) of the lungs were measured. And the mortality was recorded for 7 days. RESULTS. TNF-? and IL-6 production, NF-?B activity, TLR2 and TLR4 expression in rat lungs were increased after CLP. Ketamine at the doses of 5 mg/kg and 10 mg/kg suppressed CLP-induced elevation of TNF-? and IL-6 production, NF-?B activity and TLR2 expression. Ketamine 0.5, 5 and 10 mg/kg inhibited TLR4 expression in sepsis. Ketamine 5mg/kg and 10 mg/kg after CLP improved the survival of rats. CONCLUSIONS. Ketamine at sub-anesthetic doses could suppress the production of inflammatory cytokines such as TNF-? and IL-6, attenuate NF-?B activity, and inhibit TLR2 and TLR4 expression in polymicrobial sepsis. These anti-inflammatory effects of ketamine may correlate with improved survival in sepsis.
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