Possible involvement of macrophage-mediated hepatocytotoxicity in chronic active hepatitis: the induction of liver cell injury by culture supernatant of MAF-activated macrophages.

When peripheral blood lymphocytes from patients with various types of hepatitis were stimulated in vitro with liver specific protein, lymphocyte transformation and MIF production were demonstrated in many cases, especially in chronic active hepatitis. The culture supernatant of these activated lymphocytes was also shown to contain MAF, a kind of lymphokine, which activated the peritoneal macrophages of guinea pigs. When the culture fluid of MAF-activated macrophages was added to isolated liver cells, a significant inhibition of their albumin biosynthesis was detected. The active principle which caused the impairment of liver function was fractionated by gel filtration using a Sephadex G-75 column, and it was found that the active material was a protein-like substance with a molecular weight of about 10,000-40,000. The results suggest the possibility that the soluble substance released from the activated macrophage may be involved at least partially in the immunological pathogenesis of chronic active hepatitis among many other immunological processes.