The role of chemokines as inflammatory mediators in chronic hepatitis C virus infection

Abstract

Hepatitis C virus (HCV) is a leading cause of chronic liver disease that can progress to cirrhosis and/or hepatocellular carcinoma. Intrahepatic inflammation and liver cell injury are defining features of chronic HCV infection. Chemokines, chemotactic cytokines that attract leucocytes to inflammatory sites, may be important in the development of intrahepatic inflammation. As T-helper (Th)1 inflammatory cells, characterized by interferon (IFN)-gamma and interleukin (IL)-2 secretion, predominate in the liver during chronic HCV infection, chemokines that attract these cells might be particularly important in disease progression. In this review, we focus on the role of Th1 chemokines, which are all members of the CXC or CC subfamilies. Among the CXC chemokines, the non-ELR group comprised of IFN-gamma-inducible protein 10 (IP-10), monokine induced by IFN-gamma (Mig) and IFN-inducible T-cell-alpha chemoattractant (I-TAC), attract Th1 cells through the interaction with their receptor, CXCR3. Among the CC subfamily, Th1-associated chemokines include regulated upon activation, normal T-cell expressed and secreted (RANTES) and macrophage inflammatory proteins (MIP)1alpha and beta. These chemokines attract cells through an interaction with their receptor, CCR5. While peripheral blood and intrahepatic levels of all of these chemokines are elevated in chronic hepatitis C patients, only select chemokines have been found to be correlated with hepatic inflammation. Among the six chemokines, IP-10 has uniquely been shown to have prognostic utility as a marker of treatment outcome. In the future, chemokines might be used to monitor the natural course and progression of HCV-associated liver disease, to identify patients with a high likelihood of achieving a therapeutic response, and they may even have potential as therapeutic targets.

Association of IP-10 gene polymorphism with susceptibility to Enterovirus 71 infection

“…Thus, these chemokines have been suggested to be potential therapeutic targets in cancer, allograft rejection, diabetes, multiple sclerosis and autoimmune disorders of the thyroid (10). IP-10 has also been found to be associated with hepatic inflammation and to be a potential marker of treatment outcome (11). Previous studies have also shown that the CXCL10/IP-10 level is elevated in the sera and livers of progressed HBV carriers, and that the -1596T-201A haplotype is associated with higher CXCL10/IP-10 transcription in IFN-γ-stimulated peripheral blood mononuclear cells (5).…”

Coinfection with Hepatitis C Virus among HIV-1-Infected Individuals Increases Proinflammatory Cytokines and HIV-1 Disease Severity

“…Meanwhile, IP-10 has been a widely studied cytokine with respect to HCV infection. As the name suggests, it is a chemokine, inducible by IFN-γ [45] and produced by several cell types such as hepatocytes, NK cells, monocytes, and T-lymphocytes [46]. During HCV infection, hepatocytes produce IP-10 and circulating levels of IP-10 are known to be measurable during chronic HCV infection [37].…”

Chemokine Responses to Hepatitis C Virus and Their Impact in Mediating the Treatment Responses of Antiviral Treatment

“…Finally, in two other studies baseline levels of IP10 were associated with a negative prognostic response to treatment with peg-IFN-and ribavirin (Butera et al, 2005;Lagging et al, 2006). Interestingly, as the CCL 3-5 are produced in the portal vascular endothelium while IP-10 is produced mainly in sinusoidal endothelium and hepatocytes surrounding lobular inflammation (Zeremski et al, 2007). Fig.…”