Effect of intravenous anesthetics on spontaneous and endotoxin-stimulated cytokine response in cultured human whole blood.
BACKGROUND
Various anesthetics have been suggested to interfere with the immune system. The ability of leukocytes to express surface receptors and mediators is fundamental to a successful host defense. Therefore, the effects of intravenous anesthetics on cytokine release by leukocytes and expression of surface molecules known to modulate this response were determined.


METHODS
Concentration-dependent effects of thiopentone, etomidate, propofol, ketamine, midazolam, and fentanyl on spontaneous and endotoxin (lipopolysaccharide; 1 microg/ml)-stimulated cytokine release were studied in whole blood from volunteers (n = 6) cultured for 25 h. In addition, expression of the lipopolysaccharide-recognition molecule CD14 and the major histocompatibility complex class II molecule human leukocyte locus A system-DR (HLA-DR) on monocytes were assessed using flow cytometry.


RESULTS
All anesthetics studied elicited only minor effects on spontaneous cytokine release even at pharmacologic concentrations. However, expression density of CD14 was reduced in the presence of thiopentone, etomidate, and propofol, whereas HLA-DR was unaffected. Lipopolysaccharide-stimulated tumor necrosis factor response was inhibited by thiopentone (12.8% [median]; 7.6-18.8 [25-75 percentile]) of control, and ketamine (46.4% [median]; 44.4-56.4 [25-75 percentile]), at pharmacologic concentrations, whereas it was augmented even in the presence of low concentrations of propofol (172.3% [median]; 120.5-200.7 [25-75 percentile]). Ketamine additionally decreased the concentration of interleukin (IL)-1beta (14.8% [median]; 12.0-18.0 [25-75 percentile]). Release of IL-1 receptor antagonist (IL-1ra) was inhibited by thiopentone, etomidate, and propofol, whereas the same anesthetics increased IL-10 concentration simultaneously. Midazolam and fentanyl did not alter the concentrations of any cytokine.


CONCLUSIONS
These results suggest a complex modulation of the cytokine response by the studied anesthetics in cultured whole blood. Although effects on spontaneous cytokine release by leukocytes were negligible, some anesthetics affected their ability to respond to lipopolysaccharide.
Larsen
B
B
Department of Anesthesiology and Critical Care Medicine, University of the Saarland, Homburg/Saar, Germany.
Hoff
G
G
Wilhelm
W
W
Buchinger
H
H
Wanner
G A
GA
Bauer
M
M
D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D001558:Benzethonium / Q000494:pharmacology; D016207:Cytokines / Q000097:blood*; D004731:Endotoxins / Q000494:pharmacology*; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000097:blood; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D018950:Lipopolysaccharide Receptors / Q000097:blood; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009994:Osmolar Concentration
D018686:Anesthetics, Intravenous; D016207:Cytokines; D004731:Endotoxins; D006684:HLA-DR Antigens; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D001558:Benzethonium; C044101:endotoxin, Escherichia coli