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Bile acids inhibit endotoxin‐induced release of tumor necrosis factor by monocytes: An in Vitro study
Author(s) -
Greve Jan Willem,
Gouma Dirk J.,
Buurman Wim A.
Publication year - 1989
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840100409
Subject(s) - deoxycholic acid , tumor necrosis factor alpha , bile acid , in vitro , ursodeoxycholic acid , cholic acid , limulus amebocyte lysate , cytokine , necrosis , chemistry , pharmacology , immunology , medicine , lipopolysaccharide , biochemistry
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, chenodeoxy‐cholic 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.