Effects of ketamine on pulmonary TLR4 expression and NF-kappa Bactivation during endotoxemia in rats

The aim of the study was to investigate the effects of ketamine on pulmonary Toll-like receptor 4 (TLR4) expression and nuclear factor kappa-B (NF-kappa-B) activity in rats with endotoxemia. Rats were treated with lipopolysaccharide (LPS, 5 mg/kg) to induce endotoxemia, followed immediately by ketamine (0.5, 5 and 10 mg/kg) or 0.9% NaCl (5 ml/kg). At 1, 3 and 5 h posttreatment, TLR4 mRNA expression and NF-kappa-B activity of the rat lungs were analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and electrophoretic mobility shift assay (EMSA), respectively. LPS increased TLR4 expression and NF-kappa-B activity in the rat lungs. Ketamine at the dose levels of 5 and 10 mg/kg suppressed the LPS-induced elevation of TLR4 expression and NF-kappa-B activity. Ketamine alone had no effect on either one of them. The present study revealed that ketamine could inhibit pulmonary NF-kappa-B activity during endotoxemia in rats, and this antiinflammatory effect possibly acts through suppressing TLR4 expression.