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

• Published in: Immunology 2009-09, Vol.128 (1pt2), p.e514-e522
• Main Authors: Sharma, Arpita, Chakraborti, Anuradha, Das, Ashim, Dhiman, Radha Krishan, Chawla, Yogesh
• Format: Article
• Language: English
• Subjects: Adult; cytokines; Female; Hepacivirus - immunology; hepatitis; Hepatitis C virus; Hepatitis C, Chronic - blood; Hepatitis C, Chronic - immunology; Humans; immunotherapeutics; inflammation; Interleukin-18 - blood; Liver Cirrhosis - immunology; Liver Cirrhosis - virology; Male; Middle Aged; Original; RNA, Messenger - metabolism; Up-Regulation
• ISSN: 0019-2805; 1365-2567
• DOI: 10.1111/j.1365-2567.2008.03021.x

Summary 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‐γ‐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.