Differential effects of chenodeoxycholic and ursodeoxycholic acids on expression of procoagulant activity by human monocytes.
Cell-mediated immunity is impaired during cholestasis, and there is evidence for the involvement of endogenous bile acids. The aim of this study was to evaluate the effects of individual bile acids on immunity and to determine whether monocytes are a target. The effects of bile acids on the procoagulant activity of human monocytes, a lymphocyte-dependent model of monocyte activation, were assessed. Chenodeoxycholic acid, one of the main human primary bile acids, had a concentration-dependent inhibitory effect on procoagulant activity expressed by endotoxin-stimulated mononuclear cells, with half-maximal and maximal inhibitions at 100 and 250 microM, respectively. The inhibitory concentrations were similar for the procoagulant activity of unstimulated mononuclear cells and for endotoxin-stimulated isolated monocytes. In contrast, ursodeoxycholic acid, a bile acid which has beneficial effects in cholestatic diseases, had no significant inhibitory effects at concentrations up to 250 microM. These results indicate that endogenous bile acids tend to inhibit monocyte activation, suggesting a potential role for primary endogenous bile acids in the immune defect associated with cholestasis; ursodeoxycholic acid, which is devoid of effects on the immune system, may potentially reverse cholestasis-induced immunodeficiency.
Calmus
Y
Y
Service de Chirurgie et de Transplantation Hépatique, Hôpital Cochin, Paris, France.
Podevin
P
P
Robert
A
A
Poupon
R
R
D001779:Blood Coagulation Factors / Q000096:biosynthesis*; D002478:Cells, Cultured; D002635:Chenodeoxycholic Acid / Q000494:pharmacology*; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D014580:Ursodeoxycholic Acid / Q000494:pharmacology*
D001779:Blood Coagulation Factors; D008070:Lipopolysaccharides; D002635:Chenodeoxycholic Acid; D014580:Ursodeoxycholic Acid