期刊
JOURNAL OF VIROLOGY
卷 76, 期 21, 页码 10702-10707出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.76.21.10702-10707.2002
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资金
- NCI NIH HHS [R01 CA040489, CA40489, R37 CA040489] Funding Source: Medline
- NIAID NIH HHS [R01 AI040696, AI40696] Funding Source: Medline
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-mug 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 mug of IL-18 injected repetitively, and also by a single 0.1-mug 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.
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