title: Dexmedetomidine suppresses proinflammatory mediator production in human whole blood in vitro.
abstract: BACKGROUND
  It has been demonstrated that proinflammatory mediators increase in patients with sepsis, trauma, and burns. These mediators are associated with the development of septic shock and organ dysfunction. Dexmedetomidine (DEX), a selective agonist of the α2-adrenergic receptors, is used in intensive care units for sedation. However, it still remains unclear whether DEX administration has any effects on the production of proinflammatory mediators. In this study, we investigated the effects of DEX on lipopolysaccharide (LPS)-induced production of tumor necrosis factor α, interleukin 6 (IL-6), IL-8, and high-mobility group box 1 protein in human whole blood.
  
  
  METHODS
  Human whole blood was cultured with LPS for up to 24 hours, and LPS-induced proinflammatory mediator production was measured. Next, we tested the effect of DEX on whole blood proinflammatory mediator production. Human whole blood was cultured with LPS and various concentrations of DEX for 12 hours. Then, we investigated the influence of yohimbine, an antagonist of the α2-adrenergic receptors, on the effects of DEX. The effect of DEX on necrosis factor κB (NFκB) activation was also investigated.
  
  
  RESULTS
  DEX suppressed tumor necrosis factor α, IL-6, IL-8, and high-mobility group box 1 protein production in human whole blood. The suppressing effects of DEX on proinflammatory mediator production were reversed by yohimbine. The results suggested that the mechanism for the suppressive effects of DEX on proinflammatory mediator production is meditated via α2-adrenergic receptors. These effects of DEX also include an inhibitory effect on NFκB activation.
  
  
  CONCLUSIONS
  We demonstrate the suppressing effect of DEX on inflammatory mediator production in human whole blood after LPS stimulation. The mechanism for the suppressive effect of DEX on proinflammatory mediator production may be through the α2-adrenergic receptors and NFκB inhibition.
authors.affiliation: Department of Anesthesiology, University of Occupational and Environmental Health, Kitakyushu, Japan. takasi-k@med.uoeh-u.ac.jp
authors.forename: Takashi
authors.initials: T
authors.lastname: Kawasaki
authors.forename: Chika
authors.initials: C
authors.lastname: Kawasaki
authors.forename: Masaya
authors.initials: M
authors.lastname: Ueki
authors.forename: Kohtaro
authors.initials: K
authors.lastname: Hamada
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Habe
authors.forename: Takeyoshi
authors.initials: T
authors.lastname: Sata
mesh_terms: D000328:Adult; D020927:Dexmedetomidine / Q000494:pharmacology*; D024243:HMGB1 Protein / Q000096:biosynthesis*; D006801:Humans; D066298:In Vitro Techniques; D015850:Interleukin-6 / Q000096:biosynthesis*; D016209:Interleukin-8 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D016328:NF-kappa B / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D024243:HMGB1 Protein; D015850:Interleukin-6; D016209:Interleukin-8; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D015016:Yohimbine; D020927:Dexmedetomidine