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  • Title: Effects of ketamine on levels of cytokines, NF-kappaB and TLRs in rat intestine during CLP-induced sepsis.
    Author: Yu M, Shao D, Liu J, Zhu J, Zhang Z, Xu J.
    Journal: Int Immunopharmacol; 2007 Aug; 7(8):1076-82. PubMed ID: 17570324.
    Abstract:
    This study was designed to investigate the effects of ketamine on levels of inflammatory cytokines, nuclear factor-kappa B (NF-kappaB) and Toll-like receptors (TLRs) in rat intestine during polymicrobial sepsis, induced by cecal ligation and puncture (CLP). After the induction of sepsis or sham-operation, the rats were treated with ketamine (2.5, 5 or 10 mg/kg) or saline (10 ml/kg). At 2, 4 or 6 h post-operation, the intestinal concentrations of inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-6, were determined by enzyme-linked immunosorbent assay (ELISA). Activity of NF-kappaB in rat intestine was assessed by electrophoretic mobility shift assay (EMSA). And expressions of Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4) of rat intestine were examined by reverse transcription-polymerase chain reaction (RT-PCR). We found that TNF-alpha and IL-6 concentrations, NF-kappaB activity, TLR2 and TLR4 expressions in rat intestine were increased after CLP. At the doses of 5 and 10 mg/kg, ketamine suppressed CLP-induced elevation of IL-6. Ketamine 2.5, 5 and 10 mg/kg after CLP decreased intestinal TNF-alpha level and NF-kappaB activity, and inhibited TLR2 and TLR4 expressions as well. These results suggest that ketamine may have anti-inflammatory effects, such as suppressing the levels of inflammatory cytokines and attenuating NF-kappaB activity, during polymicrobial sepsis. And these anti-inflammatory effects possibly correlate with the inhibitory influence of ketamine on TLR2 and TLR4 expressions.
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