PMID- 12368312
OWN - NLM
STAT- MEDLINE
DCOM- 20021126
LR  - 20220224
IS  - 0022-538X (Print)
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Linking)
VI  - 76
IP  - 21
DP  - 2002 Nov
TI  - Interleukin-18 inhibits hepatitis B virus replication in the livers of transgenic 
      mice.
PG  - 10702-7
AB  - 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.
FAU - Kimura, Kiminori
AU  - Kimura K
AD  - Department of Molecular and Experimental Medicine, The Scripps Research 
      Institute, La Jolla, California 92037, USA.
FAU - Kakimi, Kazuhiro
AU  - Kakimi K
FAU - Wieland, Stefan
AU  - Wieland S
FAU - Guidotti, Luca G
AU  - Guidotti LG
FAU - Chisari, Francis V
AU  - Chisari FV
LA  - eng
GR  - R37 CA040489/CA/NCI NIH HHS/United States
GR  - CA40489/CA/NCI NIH HHS/United States
GR  - R01 CA040489/CA/NCI NIH HHS/United States
GR  - R01 AI040696/AI/NIAID NIH HHS/United States
GR  - AI40696/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Antiviral Agents)
RN  - 0 (DNA, Viral)
RN  - 0 (Interferon-alpha)
RN  - 0 (Interleukin-18)
RN  - 0 (Recombinant Proteins)
RN  - 187348-17-0 (Interleukin-12)
RN  - 77238-31-4 (Interferon-beta)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Animals
MH  - Antiviral Agents/administration & dosage/*pharmacology
MH  - DNA, Viral/analysis
MH  - Drug Synergism
MH  - Hepatitis B virus/*drug effects/genetics/physiology
MH  - Humans
MH  - Interferon-alpha/immunology
MH  - Interferon-beta/immunology
MH  - Interferon-gamma/immunology
MH  - Interleukin-12/administration & dosage/pharmacology
MH  - Interleukin-18/administration & dosage/*pharmacology
MH  - Liver/*virology
MH  - Male
MH  - Mice
MH  - Mice, Transgenic
MH  - Recombinant Proteins/administration & dosage/pharmacology
MH  - Time Factors
MH  - Virus Replication/*drug effects
PMC - PMC136645
EDAT- 2002/10/09 04:00
MHDA- 2002/11/28 04:00
PMCR- 2002/11/01
CRDT- 2002/10/09 04:00
PHST- 2002/10/09 04:00 [pubmed]
PHST- 2002/11/28 04:00 [medline]
PHST- 2002/10/09 04:00 [entrez]
PHST- 2002/11/01 00:00 [pmc-release]
AID - 0977 [pii]
AID - 10.1128/jvi.76.21.10702-10707.2002 [doi]
PST - ppublish
SO  - J Virol. 2002 Nov;76(21):10702-7. doi: 10.1128/jvi.76.21.10702-10707.2002.