Immunosuppressive effects of endotoxins and bile acids in vivo in the rat

Abstract

Cell-mediated immunity is impaired during cholestasis. The aim of this study was to evaluate in vivo the effects on this immune defect of high serum levels of endotoxin and bile acids. Heterotopic cardiac allotransplantations were performed in the DA/Lewis rat combination. Cholestasis, induced by ligation/section of the common bile duct, was responsible for a significant delay in the rejection time (16 +/- 0.5 vs. 7.1 +/- 0.4 days in controls, P < 0.01). Elimination of Gram-negative intestinal bacteria from cholestatic rats by a vancocin/colimycin/tobramycin (VCT) mixture induced a significant reduction in endotoxin levels and a reduction in rejection times (9.5 +/- 1.0 days, P < 0.01) that remained, however, significantly longer than those of controls (P < 0.05). Oral administration of chenodeoxycholic acid in non-cholestatic rats significantly enhanced the serum concentration of total bile acids (60.6 +/- 15.3 mumol L(-1) vs. 17.4 +/- 1.9 mol L(-1) in controls, P < 0.01) and postponed allograft rejection (10.7 +/- 0.6 days, P < 0.01 vs. controls). These data suggest that increased endotoxin level and serum bile acid concentration may play a role in the immunosuppressive effect of cholestasis.