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

• Verfasst von: Manigold, Tobias [VerfasserIn]
• Verfasst von: Böcker, Ulrich [VerfasserIn]
• Verfasst von: Chen, Jingsan [VerfasserIn]
• Verfasst von: Gundt, Jutta [VerfasserIn]
• Verfasst von: Traber, Petra Sieglinde [VerfasserIn]
• Verfasst von: Singer, Manfred V. [VerfasserIn]
• Verfasst von: Rossol, Siegbert [VerfasserIn]
• Titel: 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
• Verf.angabe: Tobias Manigold, Ulrich Böcker, Jingsan Chen, Jutta Gundt, Petra Traber, Manfred V. Singer, and Siegbert Rossol
• E-Jahr: 2003
• Jahr: 08 July 2003
• Umfang: 10 S.
• Fussnoten: Gesehen am 26.04.2022
• Titel Quelle: Enthalten in: Journal of medical virology
• Ort Quelle: Bognor Regis [u.a.] : Wiley, 1977
• Jahr Quelle: 2003
• Band/Heft Quelle: 71(2003), 1 vom: Sept., Seite 31-40
• ISSN Quelle: 1096-9071
• DOI: doi:10.1002/jmv.10445
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: ELISA
• Sach-SW: HBcAg
• Sach-SW: HBV infection
• Sach-SW: IL-18
• Sach-SW: quantitative RT-PCR
• K10plus-PPN: 1800280564

Abstract

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.