Studies on intrahepatic cholestatic: intrahepatic cholestasis induced in rats by the culture supernatant of activated lymphocytes.

When lymph node lymphocytes from sensitized guinea pigs were stimulated with a specific antigen in vitro, and their culture supernatants injected into the mesenteric vein of rats, a marked reduction of bile flow and bile secretion was seen. Gel filtration of this active principle revealed that the active material has a molecular size similar to that of the macrophage migration inhibitory factor (MIF). Histologically, dilated bile canaliculi with decreased microvilli were observed by electron microscopy in rat liver after injection of culture supernatant. No such change was observed in rats after injection of the supernatant of lymphocyte cultures prepared from non-sensitized guinea pigs. These results strongly suggest that the sensitized lymphocytes produce a factor (or factors) which causes intrahepatic cholestasis when stimulated with a specific antigen.