CXC chemokine IP-10: a key actor in liver disease?

Interferon-γ-inducible protein 10 (IP-10), or C-X-C motif chemokine (CXCL10), is a small cytokine belonging to the non-ELR CXC chemokine family. By binding to its specific receptor CXCR3, IP-10 recruits activated CXCR3+ T cells to the liver parenchyma and plays a pivotal role in liver disease initiation and progression. IP-10 is mainly secreted by hepatocytes and liver sinusoidal endothelium. Different IP-10 forms exert different functions: long-length IP-10 directs CXCR3+ T cell migration and is associated with inflammation, while short IP-10 is a CXCR3 antagonist, thereby playing protective role in liver injury. IP-10 levels are positively associated with the severity of liver inflammation, fibrosis stage and acute graft rejection. High IP-10 levels are closely related to anti-HCV therapy failure. Thus, IP-10 may be both a potential prognostic tool and a therapeutic target for the treatment of patients with HCV or HIV/HCV co-infection. The purpose of this review is to highlight the growing advances in basic knowledge and clinical interest of IP-10 in liver disease.