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

Abstract

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-gamma 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-gamma-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-gamma-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-gamma 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-gamma 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-gamma 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.

• Authors: Sabine Mihm, Stefan Schweyer, Giuliano Ramadori
• Journal: Journal of medical virology (J Med Virol) Vol. 70 Issue 4 Pg. 562-70 (Aug 2003) ISSN: 0146-6615 [Print] United States
• PMID: 12794718 (Publication Type: Journal Article)
• Copyright: Copyright 2003 Wiley-Liss, Inc.

Chemical References

• Chemokine CXCL10
• Chemokines, CXC
• Interleukin-18
• RNA, Messenger
• Interferon-gamma

Topics

• Adolescent
• Adult
• Chemokine CXCL10
• Chemokines, CXC (blood, genetics, metabolism)
• Female
• Hepatitis B (immunology, physiopathology)
• Hepatitis C, Chronic (immunology, physiopathology)
• Humans
• Interferon-gamma (blood, genetics, metabolism)
• Interleukin-18 (blood, genetics, metabolism)
• Liver (immunology, metabolism)
• Male
• Middle Aged
• RNA, Messenger (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction