Immunological studies on drug-induced allergic hepatitis

Abstract

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.

Drug-Induced Lymphocyte Transformation in Peripheral Lymphocytes from Patients with Drug Eruptions

“…However, in patients with drug eruptions, who did not show any liver injury, the addition of liver subcellular component did not induce lymphocyte transformation [5]. Therefore, it seems possible that in drug-induced allergic hepatitis, a hapten-carrier complex may be formed in the liver.…”

“…In drug-induced allergic hepatitis, a positive lymphocyte transformation has been shown in vitro when peripheral lymphocytes were stimulated with the suspected drug in the presence of rat liver microsome fraction or soluble fraction [5].…”

Allergic Hepatitis in Guinea Pigs Induced by 2,4,6-Trinitrophenyl Liver Protein Conjugate

“…Therefore, in drug-induced allergic hepatitis, if the drugs are combined with par ticular liver components or substances similar to liver components in the patients scrum, hapten-carrier conjugates may be formed and the immunological re sponse of lymphocytes will occur in vitro. From this standpoint, Mizoguchi et al [6] showed that the addi tion of various liver components instead of autolo gous patient serum to the culture elicited druginduced lymphocyte transformation more efficiently than autologous serum. In their study, the use of kid ney components instead of liver components had no effect on eliciting transformation.…”