Experimental immunological intrahepatic cholestasis model.

Heat-killed Propionibacterium acnes (P. acnes) was intravenously injected into tuberculin-sensitized guinea pigs, and 7 days later, purified protein derivative (PPD) was also injected intravenously resulting in marked reductions in bile flow and bile acid excretion. Serum levels of bile acids and cholesterol were increased, and the activities of alkaline phosphatase (ALK-p) and leucine aminopeptidase (LAP) were also elevated. Histological examination revealed dilatation of bile canaliculi and diminution of microvilli. These results indicated that intrahepatic cholestasis was induced. These pathological changes were not detected in guinea pigs in which PPD was not injected. In this experimental model, the tuberculin-sensitized lymphocytes were infiltrated into the liver by P. acnes injection and the cholestatic factor was produced by PPD injection, resulting in the induction of intrahepatic cholestasis.