[In vitro cytokine production in patients with HBe antigen positive chronic active hepatitis receiving...

Twenty patients with HBe antigen positive, chronic active hepatitis receiving interferon-beta (HuIFN-beta) for 4 weeks were studied. Within the follow-up period (12.3 +/- 2.0 months; mean +/- SD), nine patients were seroconverted to anti-HBe positive and/or HBe antigen negative. In vitro synthesis of interleukin-1 (IL-1), interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) were determined from supernatants of peripheral blood mononuclear cells (PBMCs) cultured in the presence of lipopolysaccharide or concanavalin-A. PBMCs from patients before IFN-beta treatment secreted markedly reduced levels of IL-1 (p less than 0.01) and IFN-gamma (p less than 0.01) as compared with healthy controls. However, IFN-gamma synthesis in the patients was significantly increased (p less than 0.05) along with the IFN-beta treatment. IL-2 synthesis was similar in chronic active hepatitis B patients before and during IFN-beta treatment when compared to normal controls, but after the therapy, the elevation of IL-2 synthesis was observed in accordance with the elevation of serum AST in two cases. Nine patients who seroconverted to anti-HBe positive and/or HBe antigen negative showed the significantly lower levels of DNA polymerase before IFN-beta treatment than non-responder group. There were no other differences in sex, age, serum AST, histologic activities and cytokine production in vitro between two groups. These results indicate the presence of immunologic deficiencies in patients with HBe antigen positive chronic active hepatitis and give the rationales for the use of interferon treatment on immunologic basis.