Immunosuppressive properties of chenodeoxycholic and ursodeoxycholic acids in the mouse.
Cell-mediated immunity is impaired during cholestasis, and there is evidence that bile acids play a role in this immune defect. Ursodeoxycholic acid (UDCA), which corrects the immunological abnormalities observed in primary biliary cirrhosis, could counter the detrimental effects of the endogenous bile acids. Accordingly, we assessed the respective effects of cholestasis, chenodeoxycholic acid (CDCA), and UDCA, using mixed lymphocyte culture as a model of allogeneic immune response. CDCA induced a dose-dependent inhibition of the proliferative response (0-150 mumol/L). Mononuclear cells obtained from bile duct-ligated mice had a normal immunostimulatory effect, whereas responder cells obtained from such animals showed a profoundly impaired proliferative response, suggesting that responder T cels are the main target of the cholestasis-induced immune defect. Supplementation of cultures with exogenous interleukins partially compensated for the inhibitory effect of 25 mumol/L CDCA, but not for that of 50 mumol/L CDCA, suggesting that impaired secretion of interleukins is not the only factor involved in the effect of bile acids. In contrast to CDCA, UDCA had no inhibitory effect on the allogenic immune response at concentrations of up to 50 mumol/L.
Calmus
Y
Y
Laboratoire d'Immunologie, Faculté de Médecine Cochin-Port-Royal, Paris, France.
Weill
B
B
Ozier
Y
Y
Chéreau
C
C
Houssin
D
D
Poupon
R
R
D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D002635:Chenodeoxycholic Acid / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D007959:Lymphocyte Culture Test, Mixed; D008214:Lymphocytes / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D014580:Ursodeoxycholic Acid / Q000494:pharmacology*
D007166:Immunosuppressive Agents; D002635:Chenodeoxycholic Acid; D014580:Ursodeoxycholic Acid