In vitro effects of lymphoblastoid interferon on lymphocyte activation and cell-mediated cytolysis in patients with chronic hepatitis B virus infection

Abstract

In addition to a direct anti-viral effect, interferons have important immunological properties including effects on cell-mediated immunity and antibody production as well as cell-mediated cytolysis. In chronic hepatitis B virus infection the host immune system is important for the elimination of replicating virus and in addition to directly inhibiting hepatitis B virus replication, interferons may affect host immune responses. We investigated the effect of lymphoblastoid interferon in vitro on lymphocyte activation and cell-mediated cytolysis in patients with chronic hepatitis B virus infection. The proliferative response to the mitogen PHA was significantly impaired in patients compared to controls. In addition supernatants of cultured mononuclear cells from patients stimulated with PHA contained less interleukin-2 activity than controls while the proportion of stimulated mononuclear cells expressing the interleukin-2 receptor was also reduced in patients. Prior incubation with 10(3) U ml-1 lymphoblastoid interferon increased both interleukin-2 activity and interleukin-2 receptor expression in patients and controls, although in patients the response was less marked. In contrast the proliferative response was unaffected. Natural killer cell activity against K562 cells was similar in patients and controls which in both groups was significantly augmented by prior incubation with 10(3) U ml-1 lymphoblastoid interferon; the increase was inversely proportional to baseline activity. In contrast incubation of target or effector cells with interferon did not augment T-cell cytotoxicity against autologous hepatocytes. The effects of lymphoblastoid interferon in vitro, were modest, but subtle changes in immunological status in addition to a direct effect on viral replication may be relevant to eventual clearance of the hepatitis B virus.