Impaired specific cell-mediated immunity in experimental biliary obstruction and its reversibility by internal biliary drainage

Little is known of the effect of cholestasis on host immunity. This study evaluates lymphocytic responsiveness to PHA and LPS mitogen and to allogeneic F₃₄₄ antigen in Sprague-Dawley rats 21 days following bile duct ligation and 31 days following relief of jaundice by internal biliary drainage. Serum bilirubin level was significantly elevated in the bile duct ligated animals at Day 21 (P < 0.001) and thereafter returned to preoperative levels following internal biliary drainage. Results demonstrate depressed responsiveness to PHA (P < 0.001) and allogeneic F₃₄₄ antigen in vivo (P < 0.04) and in vitro (P < 0.02) in bile duct ligated animals as compared to sham, sham pair-fed, and normal control rats. The observed deficiency in responsiveness to T-cell-dependent mitogen and antigen cannot be explained on the basis of complicating nutritional, renal, or infective factors. Subsequent internal biliary drainage results in some improvement in T-cell responsiveness in the bile duct ligated group although recovery is not complete. B-Lymphocytic response to LPS mitogen is not affected by bile duct ligation. We conclude that cholestasis subsequent to extrahepatic biliary obstruction per se results in impairment of cell-mediated immunity in vivo. This impairment is partly reversible by internal biliary drainage. In vitro B-cell function does not appear to be affected in this model. Further study of impaired cell-mediated immunity in extrahepatic biliary obstruction will improve our understanding of the immunological status of patients with obstructive jaundice and cholestatic liver diseases.