Elevation of interleukin-18 in chronic hepatitis C: implications for hepatitis C virus pathogenesis.
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.
Sharma
Arpita
A
Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India. arpita248@yahoo.com
Chakraborti
Anuradha
A
Das
Ashim
A
Dhiman
Radha Krishan
RK
Chawla
Yogesh
Y
D000328:Adult; D005260:Female; D016174:Hepacivirus / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000097:blood / Q000276:immunology*; D006801:Humans; D020382:Interleukin-18 / Q000097:blood*; D008103:Liver Cirrhosis / Q000276:immunology / Q000821:virology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D015854:Up-Regulation
D020382:Interleukin-18; D012333:RNA, Messenger