Bile acids inhibit endotoxin-induced release of tumor necrosis factor by monocytes: an in vitro study.
Endotoxins play an important role in the pathogenesis of complications of surgery in obstructive jaundice. Preoperative treatment with orally administered deoxycholic acid prevented endotoxin-related complications, such as renal malfunction. Other bile acids, however, were less effective, and the mechanism of action is not known. Endotoxin toxicity is considered to be largely mediated by tumor necrosis factor/cachectin, a cytokine release by mononucler phagocytes. Therefore, we studied the influence of different bile acids on endotoxin-induced tumor necrosis factor production by monocytes in vitro. Bile acids inhibit tumor necrosis factor production through a direct inhibitory effect on the monocytes. Deoxycholic acid was the most effective, chenodeoxycholic acid was less effective and ursodeoxycholic acid was ineffective in the concentrations used. Bile acids did not inactivate endotoxin as measured in a chromogenic Limulus amebocyte lysate assay. The therapeutic effect of bile acids in obstructive jaundice can be explained by an inhibition of endotoxin-induced tumor necrosis factor release by mononuclear phagocytes.
Department of Surgery, Academic Hospital, University of Limburg, Maastricht, The Netherlands.
J W
JW
Greve
D J
DJ
Gouma
W A
WA
Buurman
D001647:Bile Acids and Salts / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004731:Endotoxins / Q000037:antagonists & inhibitors*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D066298:In Vitro Techniques; D008033:Limulus Test; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D001647:Bile Acids and Salts; D004731:Endotoxins; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D013755:Tetradecanoylphorbol Acetate