Use of adult human hepatocytes in primary culture for the study of clometacin-induced immunoallergic hepatitis.

To determine whether specific circulating antibodies from patients with drug-induced immunoallergic hepatitis could be involved in antibody-dependent cell-mediated cytotoxicity, an in vitro model system was set up. Normal human hepatocytes from male kidney transplantation donors were cultured and incubated with clometacin, a drug known to induce immunoallergic hepatitis in humans. After drug exposure and in the presence of lymphoid cells autologous to hepatocytes, addition of sera from patients with clometacin-induced hepatitis consistently resulted in hepatocyte injury characterized by morphological alterations and a decrease in intracellular lactate dehydrogenase and aspartate aminotransferase activities. Sera from patients with hepatitis induced by other drugs, such as cimetidine, halothane or methyldopa, were ineffective and no cytotoxicity occurred in the absence of lymphoid cells or without pre-incubation with clometacin. These results are consistent with the view that clometacin-induced hepatitis has an immunological basis and suggest that human hepatocytes co-cultured with autologous lymphoid cells represent a suitable model to study antibody-dependent cell-mediated cytotoxicity.