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.
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.
Mihm
Sabine
S
Department of Internal Medicine, Division of Gastroenterology and Endocrinology, Georg-August-Universität, Göttingen, Germany. smihm@med.uni-goettingen.de
Schweyer
Stefan
S
Ramadori
Giuliano
G
D000293:Adolescent; D000328:Adult; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006509:Hepatitis B / Q000276:immunology / Q000503:physiopathology; D019698:Hepatitis C, Chronic / Q000276:immunology* / Q000503:physiopathology*; D006801:Humans; D007371:Interferon-gamma / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D020382:Interleukin-18 / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D020382:Interleukin-18; D012333:RNA, Messenger; D007371:Interferon-gamma