@article{Yu_Shao_Yang_Feng_Zhu_Xu_2007, title={Effects of Ketamine on Pulmonary Inflammatory Responses and Survival in Rats Exposed to Polymicrobial Sepsis}, volume={10}, url={https://journals.library.ualberta.ca/jpps/index.php/JPPS/article/view/695}, DOI={10.18433/J3RP46}, abstractNote={PURPOSE. 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.}, number={4}, journal={Journal of Pharmacy & Pharmaceutical Sciences}, author={Yu, Min and Shao, Danbing and Yang, Rong and Feng, Xiaomei and Zhu, Sihai and Xu, Jianguo}, year={2007}, month={Sep.}, pages={434–442} }