Modulation of endotoxin-stimulated TNF-α gene expression by ketamine and propofol in cultured human whole blood

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-ct 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.