摘要
Interleukin-12 (IL-12) is an immunomodulatory cytokine that promotes cellular immunity. Pre-clinical data suggest that IL-12 inhibits hepatitis B virus (HBV) replication by stimulating interferon-gamma (IFN-γ ) production. We investigated whether a combination treatment with lamivudine plus recombinant human interleukin-12 (rhIL-12) will result in a greater and prolonged suppression of HBV replication in comparison with lamivudine monotherapy. Fifteen patients with HBeAg-positive chronic hepatitis B were randomized to receive either lamivudine alone for 24 weeks (group 1); combination of lamivudine for 16 weeks and rhIL-12 (200 ng/kg twice weekly), starting 4 weeks after initiation of lamivudine, for 20 weeks (group 2), or the same schedule as for group 2, with lamivudine and a higher dose of rhIL-12 (500 ng/kg, group 3). Serum HBV DNA levels, T-cell proliferation, frequency of virus-specific T-cells, and IFN-γ production were evaluated serially during and 24 weeks posttreatment. Lamivudine plus rhIL-12/500 showed greater antiviral activity than lamivudine monotherapy. However, after stopping lamivudine in groups 2 and 3, serum HBV DNA increased significantly despite continuing rhIL-12 administration. Lamivudine plus rhIL-12 treatment was associated with a greater increase in virus-specific T-cell reactivity, IFN-γ production, and an inverse correlation between the frequency of IFN-γ -producing CD4+ T-cells and viremia. The T-cell proliferative response to HBcAg did not differ between the three groups. In conclusion, the addition of IL-12 to lamivudine enhances T-cell reactivity to HBV and IFN-γ production. However, IL-12 does not abolish HBV replication in HBeAg-positive patients and does not maintain inhibition of HBV replication after lamivudine withdrawal.
Interleukin - 12 （IL - 12） is an immunomodulatory cytokine that promotes cellular immunity. Pre-clinical data suggest that IL - 12 inhibits hepatitis B virus （HBV） replication by stimulating interferon-gamma （IFN-γ） production. We investigated whether a combination treatment with lamivudine plus recombinant human interleukin - 12 （rhIL - 12） will result in a greater and prolonged suppression of HBV replication in comparison with lamivudine monotherapy. Fifteen patients with HBeAg-positive chronic hepatitis B were randomized to receive either lamivudine alone for 24 weeks （group 1） ; combination of lamivudine for 16 weeks and rhIL - 12 （200 ng/kg twice weekly）, starting 4 weeks after initiation of lamivudine, for 20 weeks （group 2）, or the same schedule as for group 2, with lamivudine and a higher dose of rhIL - 12 （500 ng/kg, group 3）. Serum HBV DNA levels, T-cell proliferation, frequency of virus-specific T-cells, and IFN-T production were evaluated serially during and 24 weeks posttreatment. Lamivudine plus rhIL- 12/500 showed greater antiviral activity than lamivudine monotherapy. However, after stopping lamivudine in groups 2 and 3, serum HBV DNA increased sig- nificantly despite continuing rhIL-12 administration.
