Dexmedetomidine inhibits inflammatory reaction in lung tissues of septic rats by suppressing TLR4/NF-κB pathway.

Dexmedetomidine has been reported to reduce mortality in septic rats. This study was designed to investigate the effects of dexmedetomidine on inflammatory reaction in lung tissues of septic rats induced by CLP. After induction of sepsis, the rats were treated with normal saline or dexmedetomidine (5, 10, or 20 µg/kg). The survival rate of septic rats in 24 h was recorded. The inflammation of lung tissues was evaluated by HE stain. The concentrations of IL-6 and TNF- α in BALF and plasma were measured by ELISA. The expressions of TLR4 and MyD88 were measured by western blotting. The activation of NF-κB in rat lung tissues was assessed by western blotting and immunohistochemistry. It was found that the mortality rate and pulmonary inflammation were significantly increased in septic rats. IL-6 and TNF-α levels in BALF and plasma, NF-κB activity, and TLR4/MyD88 expression in rat lung tissues were markedly enhanced after CLP. Dexmedetomidine (10 and 20 µg/kg) significantly decreased mortality and pulmonary inflammation of septic rats, as well as suppressed CLP-induced elevation of TNF- α and IL-6 and inhibited TLR4/MyD88 expression and NF-κB activation. These results suggest that dexmedetomidine may decrease mortality and inhibit inflammatory reaction in lung tissues of septic rats by suppressing TLR4/MyD88/NF-κB pathway.

Ketamine inhibits lipopolysaccharide-induced astrocytes activation by suppressing TLR4/NF-ĸB pathway.

BACKGROUND/AIMS: Ketamine has been reported to exert anti-inflammatory effects on astrocytes stimulated by lipopolysaccharide (LPS) in vitro and in vivo. However, the mechanism has not been elicited clearly. The aim of this study was to investigate the effects of ketamine on TLR4 expression and NF-ĸB-p65 phosphorylation, as well as the production of proinflammatory cytokines in LPS challenged astrocytes. METHODS: Astrocytes were stimulated with LPS (1µg/ ml) in the absence and presence of various concentrations of ketamine (10, 100, 1000µM). The concentrations of IL-1ß, IL-6 and TNF-α were measured by ELISA, the expression of glial fibrillary acidic protein (GFAP) in astrocytes was detected by immunofluorescence staining, the level of phosphorylated NF-ĸB p65 and the expression of TLR4 were detected by western blotting. RESULTS: LPS increased TLR4 expression and the phosphorylation of NF-ĸB p65 subunit as well as GFAP expression and the production of IL-1ß, IL-6 and TNF-α in cultured astrocytes. Ketamine (100 and 1000 µM) reduced the expression of GFAP and the production of these proinflammatory cytokines, inhibited the expression of TLR4 and attenuated the phosphorylation of NF-ĸB p65 in astrocytes challenged by LPS. CONCLUSION: The inhibitory effects of ketamine on LPS-induced astrocytes activation and inflammation response may be mediated by suppressing NF-ĸB activation through reducing the expression of TLR4.