Editorial
Copyright ©2008 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Dec 21, 2008; 14(47): 7149-7159
Published online Dec 21, 2008. doi: 10.3748/wjg.14.7149
Role of chemokines and their receptors in viral persistence and liver damage during chronic hepatitis C virus infection
Juan R Larrubia, Selma Benito-Martínez, Miryam Calvino, Eduardo Sanz-de-Villalobos, Trinidad Parra-Cid
Juan R Larrubia, Eduardo Sanz-de-Villalobos, Liver Research Unit, Department of Gastroenterology, Guadalajara University Hospital, University of Alcalá, Donante de Sangre st. 19002 Guadalajara, Spain
Selma Benito-Martínez, Miryam Calvino, Trinidad Parra-Cid, Liver Research Unit, Guadalajara University Hospital, University of Alcalá, Donante de Sangre st. 19002 Guadalajara, Spain
Author contributions: Larrubia JR and Benito-Martínez S contributed equally towards the conception and design of the review; Larrubia JR wrote and revised the manuscript; Calvino M, Sanz-de-Villalobos E, and Parra-Cid T contributed equally to the supportive work and supervision.
Supported by Grants from “Fiscam” J.C.C.M (Ayuda para proyectos de investigación en salud; PI-2007/32), “Asociación Castellana de Aparato Digestivo” (Beca ACAD; ACAD/06) and “Fundación de Investigación Médica Mutua Madrileña” (Beca Ayudas a la Investigación FMMM; 2548/2008), Spain; Selma Benito-Martínez was supported by a research grant from “Fiscam” J.C.C.M (“Perfeccionamiento y movilidad de investigadores”; MOV-2007_JI/18), Spain; Miryam Calvino was supported by a research grant from “Instituto de Salud Carlos III” (Contrato de apoyo a la investigación en el SNS’’; CA07/00157), Spain
Correspondence to: Juan R Larrubia, MD, MSc, PhD, Department of Gastroenterology, Guadalajara University Hospital, University of Alcalá, Donante de Sangre st. 19002 Guadalajara, Spain. jlarrubiam@meditex.es
Telephone: +34 -949-209200 Fax: +34-949-209259
Received: August 7, 2008
Revised: November 26, 2008
Accepted: December 2, 2008
Published online: December 21, 2008
Abstract

Chemokines produced in the liver during hepatitis C virus (HCV) infection induce migration of activated T cells from the periphery to infected parenchyma. The milieu of chemokines secreted by infected hepatocytes is predominantly associated with the T-helper/T-cytotoxic type-1 cell (Th1/Tc1) response. These chemokines consist of CCL3 (macrophage inflammatory protein-1α; MIP-1α), CCL4 (MIP-1β), CCL5 (regulated on activation normal T cell expressed and secreted; RANTES), CXCL10 (interferon-γ−inducible protein-10; IP-10), CXCL11 (interferon-inducible T-cell α chemoattractant; I-TAC), and CXCL9 (monokine induced by interferon γ; Mig) and they recruit T cells expressing either CCR5 or CXCR3 chemokine receptors. Intrahepatic and peripheral blood levels of these chemokines are increased during chronic hepatitis C. The interaction between chemokines and their receptors is essential in recruiting HCV-specific T cells to control the infection. When the adaptive immune response fails in this task, non-specific T cells without the capacity to control the infection are also recruited to the liver, and these are ultimately responsible for the persistent hepatic damage. The modulation of chemokine receptor expression and chemokine secretion could be a viral escape mechanism to avoid specific T cell migration to the liver during the early phase of infection, and to maintain liver viability during the chronic phase, by impairing non-specific T cell migration. Some chemokines and their receptors correlate with liver damage, and CXCL10 (IP-10) and CXCR3 levels have shown a clinical utility as predictors of treatment response outcome. The regulation of chemokines and their receptors could be a future potential therapeutic target to decrease liver inflammation and to increase specific T cell migration to the infected liver.

Keywords: Chemokines, Chemokine receptors, Hepatitis C virus, Viral hepatitis pathogenesis, Persistent infection, Viral escape mechanism