title: Midazolam inhibits proinflammatory mediators in the lipopolysaccharide-activated macrophage.
abstract: BACKGROUND
  Midazolam, a benzodiazepine, has a hypnotic effect and is widely used as a sedative. The role of midazolam in activation of macrophages during sepsis is not known. The aim of this study was to evaluate the antiinflammatory actions of midazolam in cultured macrophages.
  
  
  METHODS
  Using a macrophage cell line, RAW264.7 cells, the effect of midazolam on proinflammatory mediators and activation of mitogen-activated protein kinase was measured by Western blot. Nuclear factor-kappaB (NF-kappaB) activation and translocation of p65 subunit of NF-kappaB was measured using luciferase assay and immunocytochemistry. Superoxide production was measured by lucigenin chemiluminescence.
  
  
  RESULTS
  Midazolam significantly inhibited lipopolysaccharide-induced up-regulation of both cyclooxygenase 2 and inducible nitric oxide synthase in a dose-dependent manner (approximately 3-30 microm). IkappaB-alpha degradation and NF-kappaB transcriptional activity induced by lipopolysaccharide were also suppressed by the midazolam. Nuclear translocation of the p65 subunit of NF-kappaB was inhibited by midazolam. Furthermore, midazolam suppressed phosphorylation of p38 mitogen-activated protein kinase and also inhibited lipopolysaccharide-induced superoxide production in macrophages.
  
  
  CONCLUSIONS
  These results suggest that midazolam has an antiinflammatory action by inhibiting inducible nitric oxide synthase and cyclooxygenase-2 expression, possibly through suppression of NF-kappaB and p38 mitogen-activated protein kinase activation.
authors.affiliation: Department of Physiology, Chungnam National University, Daejeon, Korea.
authors.forename: Seon Nyo
authors.initials: SN
authors.lastname: Kim
authors.forename: Soo Chang
authors.initials: SC
authors.lastname: Son
authors.forename: Sang Mook
authors.initials: SM
authors.lastname: Lee
authors.forename: Cuk Seong
authors.initials: CS
authors.lastname: Kim
authors.forename: Dae Goon
authors.initials: DG
authors.lastname: Yoo
authors.forename: Sang Ki
authors.initials: SK
authors.lastname: Lee
authors.forename: Gang Min
authors.initials: GM
authors.lastname: Hur
authors.forename: Jin Bong
authors.initials: JB
authors.lastname: Park
authors.forename: Byeong Hwa
authors.initials: BH
authors.lastname: Jeon
mesh_terms: D000818:Animals; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008262:Macrophage Activation / Q000187:drug effects* / Q000502:physiology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008874:Midazolam / Q000494:pharmacology*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B; D020928:Mitogen-Activated Protein Kinases; D008874:Midazolam