Effect of midazolam on interleukin-6 mRNA expression in human peripheral blood mononuclear cells in the absence of lipopolysaccharide

Midazolam, a benzodiazepine, has an hypnotic effect via benzodiazepine rece ptors and is widely used as an anaesthetic. Recently, it has been suggested that benzodiazepines modulate cytokine responses. The purpose of the prese nt study was to evaluate the effect of midazolam on interleukin-6 (IL-6) re sponse by observing mRNA expression levels in human peripheral blood mononu clear cells (PBMCs) in the absence of lipopolysaccharide (LPS). PBMCs were isolated from healthy volunteers in endotoxin-free 0.90% sodium chloride so lution. The cells were incubated for 2 It at 37 degreesC immediately after isolation. IL-6 mRNA expression levels in the cells were quantified using r everse transcription and competitive polymerase chain reaction. It was foun d that midazolam time-dependently inhibited the IL-6 mRNA expression in PBM Cs in the absence of LPS, and significantly inhibited the IL-6 mRNA express ion at 1 mug/ml (P <0.05) or 10 mug/ml (P <0.01) in the absence of LPS. How ever, neither a specific agonist of peripheral-type benzodiazepine receptor s, Ro5-4864, nor a specific agonist of central-type benzodiazepine receptor s, clonazepam, inhibited IL-6 mRNA expression. These findings indicated a s uppression of the IL-6 response in human PBMCs by midazolam in the absence of LPS, and suggests that midazolam has its effect not via benzodiazepine r eceptors, but by another mechanism.