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 mumol/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 mumol/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 mumol/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.
Lacaille
F
F
Department of Pediatrics, Hôpital Sainte-Justine, University of Montreal, Quebec, Canada.
Paradis
K
K
D000818:Animals; D001647:Bile Acids and Salts / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis; D004347:Drug Interactions; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007376:Interleukin-2 / Q000096:biosynthesis / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D051381:Rats; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000187:drug effects; D014580:Ursodeoxycholic Acid / Q000494:pharmacology*
D001647:Bile Acids and Salts; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D014580:Ursodeoxycholic Acid; D016572:Cyclosporine; D004247:DNA