Interleukin-18 inhibits hepatitis B virus replication in the livers of transgenic mice.
Interleukin-18 (IL-18) produced by activated antigen-presenting cells stimulates natural killer (NK) cells, natural killer T (NKT) cells, and T cells to secrete gamma interferon (IFN-gamma). In this study, injection of a single 10- micro g dose of recombinant murine IL-18 rapidly, reversibly, and noncytopathically inhibited hepatitis B virus (HBV) replication in the livers of HBV transgenic mice. Furthermore, HBV replication was inhibited by as little as 1 micro g of IL-18 injected repetitively, and also by a single 0.1- micro g dose of IL-18 injected together with 1 ng of IL-12, neither of which inhibited HBV replication individually, demonstrating synergy between these cytokines in this system. The antiviral effect of IL-18 was mediated by its ability to activate resident intrahepatic NK cells and NKT cells to produce IFN-gamma and by its ability to induce IFN-alpha/beta production in the liver. These results suggest that IL-18 has the potential to contribute to the control of HBV replication during self-limited infection and that it may have therapeutic value for the treatment of patients with chronic hepatitis.
D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004279:DNA, Viral / Q000032:analysis; D004357:Drug Synergism; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D006801:Humans; D016898:Interferon-alpha / Q000276:immunology; D016899:Interferon-beta / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D018664:Interleukin-12 / Q000008:administration & dosage / Q000494:pharmacology; D020382:Interleukin-18 / Q000008:administration & dosage / Q000494:pharmacology*; D008099:Liver / Q000821:virology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D013997:Time Factors; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D004279:DNA, Viral; D016898:Interferon-alpha; D020382:Interleukin-18; D011994:Recombinant Proteins; D018664:Interleukin-12; D016899:Interferon-beta; D007371:Interferon-gamma