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

Authors
  • Lacaille, F
  • Paradis, K
Type
Published Article
Journal
Hepatology (Baltimore, Md.)
Publication Date
Jul 01, 1993
Volume
18
Issue
1
Pages
165–172
Identifiers
PMID: 8325607
Source
Medline
License
Unknown

Abstract

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.

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