title: Effect of midazolam on interleukin-6 mRNA expression in human peripheral blood mononuclear cells in the absence of lipopolysaccharide.
abstract: Midazolam, a benzodiazepine, has an hypnotic effect via benzodiazepine receptors and is widely used as an anaesthetic. Recently, it has been suggested that benzodiazepines modulate cytokine responses. The purpose of the present study was to evaluate the effect of midazolam on interleukin-6 (IL-6) response by observing mRNA expression levels in human peripheral blood mononuclear cells (PBMCs) in the absence of lipopolysaccharide (LPS). PBMCs were isolated from healthy volunteers in endotoxin-free 0.9% sodium chloride solution. The cells were incubated for 2 h at 37 degrees C immediately after isolation. IL-6 mRNA expression levels in the cells were quantified using reverse transcription and competitive polymerase chain reaction. It was found that midazolam time-dependently inhibited the IL-6 mRNA expression in PBMCs in the absence of LPS, and significantly inhibited the IL-6 mRNA expression at 1 microg/ml (P<0.05) or 10 microg/ml (P<0.01) in the absence of LPS. However, neither a specific agonist of peripheral-type benzodiazepine receptors, Ro5-4864, nor a specific agonist of central-type benzodiazepine receptors, clonazepam, inhibited IL-6 mRNA expression. These findings indicated a suppression 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 receptors, but by another mechanism.
authors.affiliation: Department of Dental Anesthesiology, Okayama University Hospital of Dentistry, 2-5-1 Shikata-cho, Okayama 700-8525, Japan. miyawaki@md.okayama-u.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Miyawaki
authors.forename: N
authors.initials: N
authors.lastname: Sogawa
authors.forename: S
authors.initials: S
authors.lastname: Maeda
authors.forename: A
authors.initials: A
authors.lastname: Kohjitani
authors.forename: M
authors.initials: M
authors.lastname: Shimada
mesh_terms: D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D000927:Anticonvulsants / Q000494:pharmacology; D001570:Benzodiazepinones / Q000494:pharmacology; D001667:Binding, Competitive; D002470:Cell Survival; D002478:Cells, Cultured; D002998:Clonazepam / Q000494:pharmacology; D003292:Convulsants / Q000494:pharmacology; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D058785:GABA-A Receptor Agonists; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008024:Ligands; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008874:Midazolam / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
chemical_list: D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D001570:Benzodiazepinones; D003292:Convulsants; D018076:DNA, Complementary; D058785:GABA-A Receptor Agonists; D015850:Interleukin-6; D008024:Ligands; D008070:Lipopolysaccharides; D012333:RNA, Messenger; C028513:4'-chlorodiazepam; D002998:Clonazepam; D008874:Midazolam