Expression of the chemokine IP-10 correlates with the accumulation of hepatic IFN-γ and IL-18 mRNA in chronic hepatitis C but not in hepatitis B

• Published in: Journal of medical virology 2003-08, Vol.70 (4), p.562-570
• Main Authors: Mihm, Sabine, Schweyer, Stefan, Ramadori, Giuliano
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Biological and medical sciences; Chemokine CXCL10; Chemokines, CXC - blood; Chemokines, CXC - genetics; Chemokines, CXC - metabolism; CXCL10; Female; Hepatitis B - immunology; Hepatitis B - physiopathology; hepatitis B virus (HBV); hepatitis C virus (HCV); Hepatitis C, Chronic - immunology; Hepatitis C, Chronic - physiopathology; Human viral diseases; Humans; Infectious diseases; interferon gamma (IFN-γ); interferon gamma inducible protein 10 (IP-10; interferon gamma inducible protein 10 (IP‐10, CXCL10); Interferon-gamma - blood; Interferon-gamma - genetics; Interferon-gamma - metabolism; interleukin-18 (IL-18); Interleukin-18 - blood; Interleukin-18 - genetics; Interleukin-18 - metabolism; Liver - immunology; Liver - metabolism; Male; Medical sciences; Middle Aged; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; RNA, Messenger - metabolism; Viral diseases; Viral hepatitis
• ISSN: 0146-6615; 1096-9071
• DOI: 10.1002/jmv.10431

The pathogenesis of hepatitis C virus‐induced chronic liver disease is still poorly understood. Previous studies revealed enhanced hepatic expression of the Th1 prototype cytokine IFN‐γ in individuals with chronic hepatitis C. In accordance with several animal models of experimentally induced hepatitis, a Th1 lymphocyte driven inflammatory process, which involves newly infiltrated as well as resident monocytes/macrophages, has been proposed. An involvement of the interferon‐γ‐inducible chemokine IP‐10, which is chemoattractive for stimulated Th1 cells and monocytes, is also suggested. Using an HBV transgenic mouse model, a reduction of hepatic infiltration and liver disease was achieved recently by administration of antibodies directed against the interferon‐γ‐inducible chemokine Mig and against IP‐10. In the present study, expression of IP‐10 was investigated both in serum and in the liver of patients with chronic hepatitis C and hepatitis B. Patients with liver diseases of non‐viral etiologies served as controls. IP‐10 expression was highest in hepatitis C. In chronic hepatitis C, but not in chronic hepatitis B nor in liver disorders unrelated to viral infections, IP‐10 expression was strongly correlated with the amount of transcripts for IFN‐γ and to the amount of transcripts for the constitutively expressed macrophage derived cytokine IL‐18. Hepatic inflammatory activity, however, was found to be associated more closely with IFN‐γ than with IP‐10 or IL‐18 mRNA expression. The data support the hypothesis that IP‐10 is responsible for the recruitment of Th cells and monocytes in chronic hepatitis C, and suggest that its role in chronic hepatitis B is less determining. Moreover, they deliver additional support for the view that IFN‐γ still has to be considered as a mediator that determines the outcome of inflammation, e.g., via its ability to activate IL‐18 expressing cells and to initiate a delayed type hypersensitivity reaction. J. Med. Virol. 70:562–570, 2003. © 2003 Wiley‐Liss, Inc.