Studies on drug-induced allergic intrahepatic cholestasis--hepatic cholestasis induced in dogs by lymphocyte culture supernatant.

When peripheral lymphocytes from patients with drug-induced allergic intrahepatic cholestasis were stimulated with a specific drug in vitro in the presence of a liver microsome fraction or soluble liver specific antigen fraction, lympholine production was seen in many cases. By the injection of culture supernatant of stimulated lymphocytes into the mesentery vein of dogs, cholestasis was induced in the liver, chiefly in the central zones of lobules. However, no cholestasis could be observed in dogs administered the supernatants of lymphocyte cultures prepared from normal individuals in the presence of drugs. Moreover, only slight swelling of the hepatocytes was observed in the liver when normal lymphocytes were stimulated with PHA-P and culture supernatant was injected into the mesentery vein of dogs. These results suggest that sensitized lymphocytes may produce a factor (or factors) by stimulation with a specific drug-carrier and this factor (or factors) causes cholestasis in the liver.