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

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.

Intestinal crosstalk between bile acids and microbiota in irritable bowel syndrome

“…37 Interestingly, the steroidal nucleus of UDCA binds to polar domains and conjugate domains bound to the membrane interface, stabilizing the membrane structure. 37 A study has shown that DCA and CDCA treatment could induce cytoskeletal rearrangement at the level of tight junctions, leading to increased paracellular permeability. 38 BAs exhibit immunosuppressant effects on cell-mediated immunity and macrophage function.…”

“…38 BAs exhibit immunosuppressant effects on cell-mediated immunity and macrophage function. 37 UDCA and its conjugates reduce interleukin-2 (IL-2) production by 35% to 60% and inhibit the proliferation of the IL-2-dependent cell line CTLL-2. 37 CDCA promotes colonic fluid and electrolyte secretion, leading to diarrhea associated with BAM.…”

“…37 UDCA and its conjugates reduce interleukin-2 (IL-2) production by 35% to 60% and inhibit the proliferation of the IL-2-dependent cell line CTLL-2. 37 CDCA promotes colonic fluid and electrolyte secretion, leading to diarrhea associated with BAM. Administration of study has shown that DCA is positively correlated with 5-hydroxytryptamine (5-HT) production.…”

“…BAs were considered to be involved in the modulation of the intestinal epithelial barrier. In the millimole range, CDCA and DCA may induce cell damage due to membrane solubilization 37 . Interestingly, the steroidal nucleus of UDCA binds to polar domains and conjugate domains bound to the membrane interface, stabilizing the membrane structure 37 .…”

“…In the millimole range, CDCA and DCA may induce cell damage due to membrane solubilization 37 . Interestingly, the steroidal nucleus of UDCA binds to polar domains and conjugate domains bound to the membrane interface, stabilizing the membrane structure 37 . A study has shown that DCA and CDCA treatment could induce cytoskeletal rearrangement at the level of tight junctions, leading to increased paracellular permeability 38 .…”