title: Modulation of endotoxin-stimulated TNF-alpha gene expression by ketamine and propofol in cultured human whole blood.
abstract: OBJECTIVE
  Anesthetic agents have direct and indirect effects on immunocompetent cells but the molecular mechanisms of direct interactions are largely unknown. Therefore, the effect of propofol and ketamine on TNF-alpha gene expression was studied in cultured blood from healthy volunteers.
  
  
  METHODS
  TNF-alpha was measured in blood cultured in the absence or presence of propofol or ketamine after stimulation with E. coli endotoxin. TNF-alpha concentrations were correlated with the expression of TNF-alpha mRNA in mononuclear cells. The half-life of TNF-alpha mRNA was assessed after addition of actinomycin D, an inhibitor of DNA-directed RNA synthesis.
  
  
  RESULTS
  Propofol increased TNF-alpha mRNA (+42%) and protein (+44%) response while the addition of ketamine attenuated the TNF-alpha mRNA (-31%) and protein (-53%) response. The half-life of TNF-alpha mRNA was unaffected by the anesthetics.
  
  
  CONCLUSIONS
  These data suggest that propofol and ketamine have opposite effects on transcription of the TNF-alpha gene. While the effects of propofol were observed with concentrations corresponding to an induction bolus, the effects of ketamine were restricted to higher concentrations.
authors.affiliation: Klinik für Anaesthesiologie und Intensivmedizin der Universität des Saarlandes, Homburg/Saar.
authors.forename: G
authors.initials: G
authors.lastname: Hoff
authors.forename: I
authors.initials: I
authors.lastname: Bauer
authors.forename: B
authors.initials: B
authors.lastname: Larsen
authors.forename: M
authors.initials: M
authors.lastname: Bauer
mesh_terms: D000778:Anesthetics, Dissociative / Q000494:pharmacology*; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D015152:Blotting, Northern; D002478:Cells, Cultured; D003609:Dactinomycin / Q000494:pharmacology; D004731:Endotoxins / Q000494:pharmacology*; D006207:Half-Life; D006801:Humans; D007649:Ketamine / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D015742:Propofol / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
chemical_list: D000778:Anesthetics, Dissociative; D018686:Anesthetics, Intravenous; D004731:Endotoxins; D008070:Lipopolysaccharides; D019384:Nucleic Acid Synthesis Inhibitors; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D003609:Dactinomycin; C044101:endotoxin, Escherichia coli; D007649:Ketamine; D015742:Propofol