Effects of bile acids on the humoral immune response - A mechanistic approach

Whereas bile acids in excess depress the cell-mediated immune response, the ir effects on the humoral response have been little investigated. The aim o f this study was to investigate the effects of bile acids on immunoglobulin production. Human peripheral blood mononuclear cells were stimulated for 5 days by Staphylococcus aureus Cowan I (SAC-I). Immunoglobulins, were measu red in the supernatants and cell lysates using ELISA. We found that bile ac ids inhibited IgM production in a dose-dependent manner. The inhibitory eff ects of 50 muM chenodeoxycholic acid (CDCA) and its glyco- and tauro-conjug ates (62, 53 and 51%, respectively) were stronger than those of ursodeoxych olic acid (UDCA) and its conjugates (45, 40 and 34%, respectively). The inh ibition of IgG production by CDCA and UDCA was weak (23 and 12%, respective ly, at 50 LM). IgA production was not modified. The inhibition of intracell ular IgM concentration paralleled that observed in the secreted compartment . By contrast, CDCA enhanced intracellular concentration of IgG. In the abs ence of significant necrosis or apoptosis, CDCA-mediated inhibition of SAC- I-induced IgM production was significantly correlated to the ability of the bile acid to inhibit cell proliferation (r=0.98; p <0.05). In conclusion, we showed that hydrophobic bile acids strongly depress the primary humoral response. This effect resulted from both an inhibition of cell proliferatio n, and to a lesser extent from a deficient exocytosis of immunoglobulins. ( C) 2001 Elsevier Science Inc. All rights reserved.