Elevation of interleukin-18 in chronic hepatitis C: implications for hepatitis C virus pathogenesis

Immunology. 2009 Sep;128(1 Suppl):e514-22. doi: 10.1111/j.1365-2567.2008.03021.x. Epub 2008 Nov 24.

Abstract

The outcome of hepatitis C virus (HCV) infection is determined by the interplay between the virus and the host immune response. Interleukin (IL)-18, an interferon-gamma-inducing factor, plays a critical role in the T helper type 1 (Th1) response required for host defence against viruses, and antibodies to IL-18 have been found to prevent liver damage in a murine model. The present study was conducted to investigate the possible role of IL-18 in the pathogenesis and persistence of HCV. IL-18 levels were measured in sera of 50 patients at various stages of HCV infection (resolved, chronic and cirrhosis) and compared with those of normal controls. IL-18 gene expression was studied in peripheral blood mononuclear cells (PBMC) from each group, and in liver biopsy tissue from patients with chronic hepatitis C. The mean levels of IL-18 in sera were markedly elevated in patients with chronic hepatitis and cirrhosis, and were reduced in patients with resolved HCV infection. The serum IL-18 concentrations were related to the Child-Pugh severity of liver disease in cirrhotic patients. There also existed a strong positive correlation of IL-18 levels with histological activity score and necrosis. IL-18 mRNA expression was significantly up-regulated in the PBMC of cirrhotic patients when compared with other groups, while in the liver, higher levels of IL-18 transcripts were expressed in patients with chronic hepatitis C. The results of our study indicate that IL-18 levels reflect the severity and activity of HCV infection, and may contribute to the pathogenesis and progression of liver disease associated with HCV.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Female
  • Hepacivirus / immunology*
  • Hepatitis C, Chronic / blood
  • Hepatitis C, Chronic / immunology*
  • Humans
  • Interleukin-18 / blood*
  • Liver Cirrhosis / immunology
  • Liver Cirrhosis / virology
  • Male
  • Middle Aged
  • RNA, Messenger / metabolism
  • Up-Regulation

Substances

  • Interleukin-18
  • RNA, Messenger