47 Citations (Scopus)

Abstract

Background: Effects of dexmedetomidine on regulating endotoxin-induced upregulation of inflammatory molecules were elucidated. Methods: Murine macrophages (RAW264.7 cells) were treated with lipopolysaccharide (LPS, 100 ng/mL), LPS plus dexmedetomidine (0.01, 0.1, 1, 10, or 100 μM), LPS plus dexmedetomidine plus yohimbine, or LPS plus dexmedetomidine plus idazoxan. The dosages of dexmedetomidine were chosen to correspond to 1, 10, 100, and 1000 times of clinically relevant dosages (i.e., 0.01-0.1 μM). The levels of inducible nitric oxide synthase (iNOS)/nitric oxide (NO), cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, and IL-10 were measured. Results: Dexmedetomidine at 0.01 μM did not affect iNOS expression and NO production in activated macrophages. At 1 μM, dexmedetomidine significantly inhibited iNOS expression (up to 20.8% ± 4.7%) and NO production (up to 26.2% ± 6.8%). In contrast, dexmedetomidine at 100 μM significantly enhanced iNOS expression (up to 31.5% ± 7.5%) and NO production (up to 34.9% ± 5.6%). The effects of dexmedetomidine on COX-2 expression and the production of PGE2, TNF-α, IL-1β, IL-6, and IL-10 paralleled the effects of dexmedetomidine on iNOS. Moreover, these effects were significantly reversed by both of the α2-adrenergic receptor antagonists, yohimbine, and idazoxan. Conclusions: Dexmedetomidine at clinically relevant dosages did not significantly affect the expression of inflammatory molecules in activated macrophages. In contrast, dexmedetomidine at dosages higher than clinically relevant ones posted small but significant biphasic effects (inhibiting, then enhancing) on regulating the expression of inflammatory molecules, possibly through the α2-adrenergic receptors. However, as the magnitude of changes was relatively small, these effects may not be clinically significant.

Original languageEnglish
Pages (from-to)212-219
Number of pages8
JournalJournal of Surgical Research
Volume154
Issue number2
DOIs
Publication statusPublished - Jun 15 2009

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Keywords

  • α2-adrenergic receptors
  • COX-2
  • cytokine
  • dexmedetomidine
  • endotoxin
  • iNOS

ASJC Scopus subject areas

  • Surgery

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