Effects of ketamine on levels of cytokines, NF-κB and TLRs in rat intestine during CLP-induced sepsis

This study was designed to investigate the effects of ketamine on levels of inflammatory cytokines, nuclear factor-kappa B (NF kappa B) 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-a) and interleukin (IL)-6, were determined by enzyme-linked immunosorbent assay (ELISA). Activity of NF-KB 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-a and IL-6 concentrations, NF-KB 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-KB activity, and inhibited TLR2 and TLR4 expressions as well. These results suggest that ketamine may have antiinflammatory effects, such as suppressing the levels of inflammatory cytokines and attenuating NF-KB activity, during polymicrobial sepsis. And these anti-inflammatory effects possibly correlate with the inhibitory influence of ketamine on TLR2 and TLR4 expressions. (C) 2007 Elsevier B.V. All rights reserved.