Immunological studies on chronic active hepatitis: possible involvement of macrophage-mediated cytotoxicity in its immunopathogenesis.

The possible involvement of cell-mediated immune responses to liver-specific protein in the pathogenesis of liver injury was investigated. The subjects consisted of seven patients with acute hepatitis, 12 cases with chronic active hepatitis, four cases with chronic inactive hepatitis, and three cases with liver cirrhosis. When peripheral blood lymphocytes from these patients were cultured in the presence of liver specific protein, and lymphocyte transformation was determined by measuring the uptake of [3H]thymidine into acid-insoluble materials, positive blastogenesis was seen in two cases with acute hepatitis and in six cases with chronic active hepatitis. The macrophage activating factor (MAF), a kind of lymphokine, was also detectable in the culture medium of activated lymphocytes from six patients who showed positive blastogenesis by estimating [3H]glucosamine incorporation into macrophages. Furthermore, the MAF-activated macrophages wer shown to be cytotoxic for the isolated liver cells causing marked inhibition of albumin synthesis. This macrophage-mediated cytotoxicity was detected in eight cases that showed positive lymphocyte transformation. These observations suggest that macrophage-mediated cytotoxicity plays a role in the pathogenesis of chronic active hepatitis.