The immunosuppressive effect of ursodeoxycholic acid: A comparative in vitro study on human peripheral blood mononuclear cells

Ursodeoxycholic acid is an efficient treatment for putatively immune‐mediated liver diseases, but its mechanism of action is unknown. We studied human mononuclear cell proliferation as an in vitro model for cell‐mediated immunity in the presence of ursodeoxycholic acid, its glycoconjugate and tauroconjugate and chenodeoxycholic acid at concentrations of 5, 25 and 50 μmol/L. Proliferation was inhibited in a dose‐dependent manner compared with control values (15% to 54% depending on the bile acid, concentration and mitogen used), except at 5 μmol/L where inhibition was significant with only one mitogenic stimulus of the three used. With one mitogen (phorbolester) the inhibition was additive with that of cyclosporine. The number of cell‐surface receptors studied was not modified by bile acids. Interleukin‐2 production was decreased 35% to 60% by ursodeoxycholic acid and its conjugates. The proliferation of the interleukin‐2–dependent cell line CTLL‐2 was also inhibited. The immunosuppression was reversible except at a chenodeoxycholic acid concentration of 50 μmol/L. Because bile acids are able to partition into membranes and change their properties, we speculate that this allows them to interact with cell‐surface receptors or signaling systems within the membrane or on its inner face, thus impairing their function. This would inhibit the numerous extracellular messages that lymphocytes need to proliferate. (HEPATOLOGY 1993;18:165–172).