DIFFERENTIAL-EFFECTS OF CHENODEOXYCHOLIC AND URSODEOXYCHOLIC ACIDS ONEXPRESSION OF PROCOAGULANT ACTIVITY BY HUMAN MONOCYTES

Cell-mediated immunity is impaired during cholestasis, and there is ev idence for the involvement of endogenous bile acids. The aim of this s tudy was to evaluate the effects of individual bile acids on immunity and to determine whether monocytes are a target. The effects of bile a cids on the procoagulant activity of human monocytes, a lymphocyte-dep endent model of monocyte activation, were assessed. Chenodeoxycholic a cid, one of the main human primary bile acids, had a concentration-dep endent inhibitory effect on procoagulant activity expressed by endotox in-stimulated mononuclear cells, with half-maximal and maximal inhibit ions at 100 and 250 mu M, respectively. The inhibitory concentrations were similar for the procoagulant activity of unstimulated mononuclear cells and for endotoxin-stimulated isolated monocytes. In contrast, u rsodeoxycholic acid, a bile acid which has beneficial effects in chole static diseases, had no significant inhibitory effects at concentratio ns up to 250 mu M. These results indicate that endogenous bile acids t end to inhibit monocyte activation, suggesting a potential role for pr imary endogenous bile acids in the immune defect associated with chole stasis; ursodeoxycholic acid, which is devoid of effects on the immune system, may potentially reverse cholestasis-induced immunodeficiency. (C) Journal of Hepatology.