In vitro effect of lymphoblastoid alpha-interferon on subpopulations of effector cells mediating cytotoxicity for autologous hepatocytes in hepatitis B and non-A, non-B

Abstract

Controlled clinical trials are currently under way to assess the efficacy of interferon (IFN) in hepatitis B virus (HBV) infection. In the present study, T-enriched and non-T-enriched lymphocytes from six patients with acute and six patients with chronic HBV infection were cocultured with autologous liver cells with and without alpha-IFN (lymphoblastoid) at a concentration of 1000 U/ml of culture medium, in an 18 h cytotoxicity assay. IFN produced a significant enhancement of non-T-cell cytotoxicity in patients with acute and chronic HBV infection, from 34.3 +/- 19.6% to 60.0 +/- 11.2%, P less than 0.03, and from 41.2 +/- 17.2% to 65.5 +/- 9.8%, P less than 0.01, respectively. In contrast, no significant effect was observed on T cell-mediated cytotoxicity in either group of patients. The in vitro effect of alpha-IFN was also evaluated in four patients who developed chronic non-A, non-B hepatitis following blood transfusion, but no significant stimulatory effect was noted on either T- or non-T cell cytotoxicity. Similarly, no significant increase was observed in control subjects. The significant enhancement of non-T cell cytotoxicity, but not of T-cell cytotoxicity, for autologous hepatocytes in HBV infection suggests that alpha-IFN produces a selective stimulatory effect on non-T cells. The absence of a similar effect in patients with chronic non-A, non-B hepatitis and control subjects suggests that HBV infection alters the susceptibility of hepatocytes to IFN-stimulated non-T cell damage.