PMID- 12858406
OWN - NLM
STAT- MEDLINE
DCOM- 20031007
LR  - 20181130
IS  - 0146-6615 (Print)
IS  - 0146-6615 (Linking)
VI  - 71
IP  - 1
DP  - 2003 Sep
TI  - Hepatitis B core antigen is a potent inductor of interleukin-18 in peripheral 
      blood mononuclear cells of healthy controls and patients with hepatitis B 
      infection.
PG  - 31-40
AB  - Clearance of hepatitis B virus infection (HBV) infection implies a polyclonal 
      vigorous T-helper 1 (Th1) and cytotoxic T-lymphocyte (CTL) response. 
      Interleukin-18 (IL-18), a monokine that shares functional abilities with IL-12, 
      is a potent inductor of interferon-gamma (IFN-gamma) by Th1 and natural killer 
      (NK) cells. However, the role and regulation in HBV infection of IFN-gamma have 
      not been defined. This study therefore sought to determine hepatitis B core 
      antigen (HBcAg)-mediated regulation of IL-18 production in peripheral blood 
      mononuclear cells (PBMCs) from healthy controls (HC) and patients with chronic 
      hepatitis B (CHB) or acute hepatitis B (AHB); 31 HC, 27 patients with CHB and 8 
      patients with AHB infection were included in the study. HBcAg-mediated induction 
      of IL-18 was determined by quantitative reverse transcription-polymerase chain 
      reaction (RT-PCR) and specific enzyme-linked immunosorbent assay (ELISA). HBcAg 
      induced IL-18 gene transcription and dose-dependent secretion of mature IL-18 
      protein in HC, CHB, and AHB. HBcAg-dependent IL-18 levels were abrogated by 
      inhibition of Caspase-1, but not by blockade of CD40-CD154 interaction. Serum 
      levels of IFN-gamma correlated inversely with viremia in patients with CHB (rho = 
      - 0.54, P < 0.05), but not with serum levels of IL-12 or IL-18. Interestingly, in 
      PBMCs of HBeAg-negative patients, HBcAg induced significantly higher amounts of 
      IL-18 than in those of HBeAg-positive patients. A variant, lacking the 
      histone-like arginine-rich domain, did not induce IL-18 in either HC or CHB in 
      vitro. Taken together, these results indicate that HBcAg induces IL-18 secretion 
      by induction of Caspase-1. Differential regulation in HBeAg-negative and positive 
      patients suggests an important role of IL-18 in CHB infection.
CI  - Copyright 2003 Wiley-Liss, Inc.
FAU - Manigold, Tobias
AU  - Manigold T
AD  - Department of Medicine II, Gastroenterology/Hepatology/Infectious Diseases, 
      University Hospital Mannheim, Mannheim, Germany. manigold@nih.gov
FAU - Bocker, Ulrich
AU  - Bocker U
FAU - Chen, Jingsan
AU  - Chen J
FAU - Gundt, Jutta
AU  - Gundt J
FAU - Traber, Petra
AU  - Traber P
FAU - Singer, Manfred V
AU  - Singer MV
FAU - Rossol, Siegbert
AU  - Rossol S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Med Virol
JT  - Journal of medical virology
JID - 7705876
RN  - 0 (Hepatitis B Core Antigens)
RN  - 0 (Hepatitis B e Antigens)
RN  - 0 (Interleukin-18)
RN  - 187348-17-0 (Interleukin-12)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Adult
MH  - Female
MH  - Gene Expression Regulation
MH  - Hepatitis B/*immunology
MH  - Hepatitis B Core Antigens/*immunology
MH  - Hepatitis B e Antigens/immunology
MH  - Hepatitis B virus/*immunology
MH  - Humans
MH  - Interferon-gamma/blood
MH  - Interleukin-12/blood
MH  - Interleukin-18/*blood/genetics/immunology/metabolism
MH  - Leukocytes, Mononuclear/immunology/*metabolism
MH  - Male
MH  - Middle Aged
MH  - Transcription, Genetic
EDAT- 2003/07/15 05:00
MHDA- 2003/10/08 05:00
CRDT- 2003/07/15 05:00
PHST- 2003/07/15 05:00 [pubmed]
PHST- 2003/10/08 05:00 [medline]
PHST- 2003/07/15 05:00 [entrez]
AID - 10.1002/jmv.10445 [doi]
PST - ppublish
SO  - J Med Virol. 2003 Sep;71(1):31-40. doi: 10.1002/jmv.10445.