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 endotoxininduced 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 endotoxininduced tumor necrosis factor release by mononuclear phagocytes.
Surgery in patients with biliary obstruction is associated with increased morbidity and mortality (1, 2). In jaundiced patients, a high incidence of endotoxemia was found that correlated with the high complication rate in these patients (3-7). Therefore, endotoxins are considered to play an important role in the pathogenesis of several complications (1, 2, 8). A possible cause for endotoxemia in jaundiced patients is the absence of bile acids in the bowel lumen, resulting in an enhanced absorption of endotoxins (1,9, 10).
Preoperative treatment with orally administered bile acids prevented renal complications in jaundiced patients (1, 11-13). Furthermore, bile acids reduced mortality in rats with experimental biliary obstruction, challenged with a high dose of oral endotoxin (1). The beneficial effect of bile acids was suggested to be an inactivation, or a prevention of the absorption, of gut-derived endotoxins. However, whereas deoxycholic acid and taurocho-