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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

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-γ (IFN-γ) by Th1 and natural killer (N...

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Main Authors: Manigold, Tobias (Author) , Böcker, Ulrich (Author) , Chen, Jingsan (Author) , Gundt, Jutta (Author) , Traber, Petra Sieglinde (Author) , Singer, Manfred V. (Author) , Rossol, Siegbert (Author)
Format: Article (Journal)
Language:English
Published: 08 July 2003
In: Journal of medical virology
Year: 2003, Volume: 71, Issue: 1, Pages: 31-40
ISSN:1096-9071
DOI:10.1002/jmv.10445
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1002/jmv.10445
Verlag, lizenzpflichtig, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/jmv.10445
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Author Notes:Tobias Manigold, Ulrich Böcker, Jingsan Chen, Jutta Gundt, Petra Traber, Manfred V. Singer, and Siegbert Rossol
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Summary: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-γ (IFN-γ) by Th1 and natural killer (NK) cells. However, the role and regulation in HBV infection of IFN-γ 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-γ correlated inversely with viremia in patients with CHB (ρ = − 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. J. Med. Virol. 71:31-40, 2003. © 2003 Wiley-Liss, Inc.
Item Description:Gesehen am 26.04.2022
Physical Description:Online Resource
ISSN:1096-9071
DOI:10.1002/jmv.10445

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