Role of interleukin-1 in the depression of liver drug metabolism by endotoxin.
Endotoxin-resistant C3H/HeJ mice were used to test the hypothesis that a macrophage product, possibly interleukin-1, might mediate the depression of liver cytochrome P-450-dependent drug metabolism in endotoxin-treated mice. Depression of liver drug metabolism by endotoxin was observed in normal mice (C3H/HeN) but not in C3H/HeJ mice. Serum transfer experiments demonstrated that a serum factor was responsible for the depression of liver drug metabolism. Experiments of passive transfer of peritoneal macrophages showed that this endotoxin-induced factor might be a macrophage product. In vitro experiments showed that endotoxin-stimulated monocytes produced a factor that depressed cytochrome P-450-dependent metabolism in cultured hepatocytes. Homogeneous human monocyte and recombinant interleukin-1 also depressed liver drug metabolism both in vivo and in vitro, suggesting that this macrophage product might be involved in the regulation of liver function by the immune system.
D015660:7-Alkoxycoumarin O-Dealkylase; D000818:Animals; D001427:Bacterial Toxins / Q000494:pharmacology; D001711:Biotransformation; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004731:Endotoxins / Q000494:pharmacology*; D007249:Inflammation / Q000378:metabolism; D007375:Interleukin-1 / Q000502:physiology*; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism*; D008264:Macrophages / Q000502:physiology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D010105:Oxygenases / Q000378:metabolism
D001427:Bacterial Toxins; D004731:Endotoxins; D007375:Interleukin-1; D008070:Lipopolysaccharides; D003577:Cytochrome P-450 Enzyme System; D010105:Oxygenases; D015660:7-Alkoxycoumarin O-Dealkylase