Published online before print June 16, 2003

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(Journal of Leukocyte Biology. 2003;74:360-369.)
© 2003 by Society for Leukocyte Biology

Expression of the chemokine IP-10 (CXCL10) by hepatocytes in chronic hepatitis C virus infection correlates with histological severity and lobular inflammation

Charles E. Harvey^*, Jeffrey J. Post, Patricia Palladinetti, Anthony J. Freeman^*, Rosemary A. Ffrench, Rakesh K. Kumar, George Marinos^* and Andrew R. Lloyd^,1

^* Viral Hepatitis Research Unit, Department of Gastroenterology, Prince of Wales Hospital, Sydney, New South Wales, Australia; and
Inflammation Research Unit, Department of Pathology, and
Department of Immunology and Infectious Diseases, Sydney Children’s Hospital, and the School of Women’s and Children’s Health, University of New South Wales, Sydney, Australia

¹Correspondence: University of NSW, Inflammation Research Unit, School of Medical Sciences, Sydney, NSW 2052, Australia. E-mail: A.lloyd{at}unsw.edu.au

The factors influencing lymphocyte trafficking to the liver lobule during chronic hepaititis C virus (HCV) infection are currently not well defined. Interferon--inducible protein 10 (IP-10), a chemokine that recruits activated T lymphocytes, has recently been shown by in situ hybridization to be expressed in the liver during chronic HCV infection. This study sought to define the cellular source of IP-10 in the liver by immunohistochemistry, to examine the expression of its receptor, CXCR3, on T lymphocytes isolated from blood and liver tissue, and to correlate IP-10 expression with the histological markers of inflammation and fibrosis. IP-10 was expressed by hepatocytes but not by other cell types within the liver, and the most intense immunoreactivity was evident in the areas of lobular inflammation. The IP-10 receptor was expressed on a significantly higher proportion of T lymphocytes in the liver compared with blood. CD8 T lymphocytes, which predominate in the liver lobule, were almost uniformly CXCR3-positive. The expression of IP-10 mRNA correlated with lobular necroinflammatory activity but not with inflammation or fibrosis in the portal tracts. These findings suggest that IP-10 may be induced by HCV within hepatocytes and may be important in the pathogenesis of chronic HCV infection, as recruitment of inflammatory cells into the lobule is an important predictor of disease progression.

Key Words: pathogenesis • liver • trafficking

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