Studies on intrahepatic cholestasis in drug-induced allergic hepatitis: intrahepatic cholestasis induced in the rat by the culture supernatant of activated lymphocytes.

A marked reduction in bile flow and bile acid excretion was whenever peripheral lymphocytes from patients with drug-induced allergic intrahepatic cholestasis were stimulated with a specific drug in vitro in the presence of a soluble liver-specific antigen fraction, and their culture supernatant injected into the mesenteric vein of rats. A gel filtration study of the active fraction of the supernatant that caused a reduction in bile flow, suggested that the molecular size of this active principle is similar to that of the macrophage migration inhibitory factor (MIF). Histologically, dilated bile canaliculi with decreased microvilli were observed via electron microscopy in rat liver after injection of culture supernatant. No such changes were observed in rats after injection of the supernatant of a lymphocyte culture similarly prepared from normal individuals. These results strongly suggested that sensitized lymphocytes obtained from patients with drug-induced intrahepatic cholestasis produce a factor (of factors) causing cholestasis when stimulated with a specific drug in the presence of liver-specific antigen fractions.