Effects of dexmedetomidine on early and late cytokines during polymicrobial sepsis in mice

Abstract

We investigated whether dexmedetomidine provided protective effects on cecal ligation and puncture (CLP)-induced septic mice, through suppressing the expression of pro-inflammatory cytokines [tumor necrosis factor-α (TNF-α) and interlukin-6 (IL-6)] and high mobility group box 1 (HMGB1). The model of sepsis was set up by CLP in 136 male BALB/c mice (40 mice for survival studies and 96 for cytokine studies) which were divided into four groups, including a C, CLP, DEX+CLP and CLP+DEX group. The serum levels of TNF-α, IL-6 and HMGB1 were detected at 6, 12, 24 and 48h after operations, and lung HMGB1 mRNA were analyzed at 24 and 48h. The mortality rates were calculated 7days after the operations. The mortality rates 7days after operations were significantly lower in the CLP+DEX (50%) and DEX+CLP (30%) groups than in the CLP group (90%). Serum concentrations of IL-6 and TNF-α decreased significantly in dexmedetomidine administration groups compared with the CLP group. The levels of HMGB1 and lung HMGB1 mRNA were lower in the dexmedetomidine administration groups than in the CLP group. There was a significant correlation between lung HMGB1 mRNA and serum HMGB1(r=0.858). Dexmedetomidine could reduce the mortality rate and inhibit pro-inflammatory cytokine responses during polymicrobial sepsis in mice.