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

Publisher Website
Google Scholar
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.
Funding Information
  • Medical Faculty of Mannheim