Immunological studies on drug-induced allergic hepatitis--hepatocellular injury by macrophage-mediated cytotoxicity

When the peripheral blood lymphocytes from patients with drug-induced allergic hepatitis were stimulated with a specific drug in vitro in the presence of a liver cytosol fraction containing liver specific antigen, lymphocyte transformation was seen in eight out of 11 patients. The macrophage activating factor (MAF), a kind of lymphokines, was also detectable in the culture medium of activated lymphocytes from seven out of eight patients who showed positive blastogenesis evaluated the uptake of 3H-glucosamine into macrophages. MAF-activated macrophages exhibited a cytotoxic effect on separated liver cells resulting in a marked inhibition of albumin synthesis. This macrophage-mediated cytotoxicity was also observed in eight out of 11 patients who showed positive lymphocyte transformation. These observations suggest that macrophage-mediated cytotoxicity may play some role in the pathogenesis of drug-induced allergic hepatitis.