Immunopathology and therapy of chronic active hepatitis type B

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The immunopathologenesis of chronic hepatitis B is still unclear, but one of the approaches to therapy is to enhance the patient's immune response to lyse the infected cells. Interleukin 2(IL2) is a lymphokine which has an important role in the proliferation and differentiation of T lymphocytes. Recent advances in DNA technology now allow production of human recombinant IL2 (rIL2) in quantitis.We have studies the clinical and immunological effects and the antiviral activity of rIL2 in patients with chronic hepatitis B.Ten patients with HBE antigen-positive chronic active hepatitis were treated with rIL2 for 3 to 4 wk. Recombinant IL2 inhibited HBV replication during therapy as judged by decrease of serum DNA polymerase activity. FUrthermore, characteristic increases of serum aminotranserase were observed during rIL2 therapy. This rise might have been mediated by enhanced immune responses to heaptitis B virus and increased rate of lysis of the infected hepatocytes. No consisten changes … More in immmune markers such as OKT4 positive cells or OKT8 positive cells were demonstrated during or after the therapy. THe activities of natural killer cells grandually increased during therapy, although they tended to decrease within 1 wk after the start of rIL2 injections. In two responders who lost HBeAg from serum, the natural killer activity was high before the therapy, compared with nonresponders. Recombinant IL2 therapy over short periods did not result in complete clearance of hepatitis B virus. Further studies with high doses of rIL2 given over longer periods are warranted.Cell-mediated immunity to HBV antigen is considered to play an important tole in HBV infection. We stidued the proliferative response of peripheral blood cells to HBC antigen in patients with HBV infection. A significant T cell proliferative response to HBV antigen was found in patients with acute hepatitis B and some of chronic hepatitis B, suggesting the presence of HBcAg sensitized T cells. Response of CD4 positive cells to HBcAg are stronger than those of CD8 positive cells. Further studies are goinf on whether or not T coll proliferative response to HBcAg reflects cell-mediated immunity to HBv and are able to use as a marker of therapeutic efficacy. Less