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  • Title: Modulation of endotoxin-stimulated TNF-alpha gene expression by ketamine and propofol in cultured human whole blood.
    Author: Hoff G, Bauer I, Larsen B, Bauer M.
    Journal: Anaesthesist; 2001 Jul; 50(7):494-9. PubMed ID: 11496686.
    Abstract:
    AIM: 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. CONCLUSION: 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.
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