Wald Ori, Weiss Ido D, Galun Eithan, Peled Amnon
Goldyne Savad Institute of Gene Therapy, Hadassah Hebrew University Hospital, P.O. Box 12000, Jerusalem 91120, Israel.
Cytokine. 2007 Jul;39(1):50-62. doi: 10.1016/j.cyto.2007.05.013. Epub 2007 Jul 16.
Hepatitis C virus infection and its associated liver inflammatory disease is a major global health problem affecting over 170 million people worldwide. Following viral infection, multiple pro-inflammatory mediators contribute to recruitment of immune cells to the liver and to the generation of an anti-viral immune response. However, when this vigorous immune response fails to eliminate the virus, chronic infection is established. This in turn, results in an ongoing process of inflammation, regeneration and fibrosis that in many cases leads to the development of cirrhosis and of hepatocellular carcinoma. Multiple recent publications mark chemokines and their receptors as key players in leukocyte recirculation through the inflamed liver. Furthermore, chemokines may also be involved in liver regeneration, fibrosis, and in malignant transformation, which is induced by the persistence of inflammation. Accumulating data indicates that distinct chemokines and chemokine receptors may be associated with different stages of the chronic hepatitis C virus infection-associated liver disease. Multiple small molecules and peptide antagonizing chemokines and their receptors are in advanced phase 3 and phase 2 clinical trials. In the near future, such drugs are expected to enter clinical use raising the question whether they may be applicable for the treatment of chronic viral infection-associated liver disease. In this review, recent advances in understanding the role of chemokines and their receptors in the pathogenesis of chronic viral infection-associated liver disease are presented. Furthermore, the clinical implications of these novel findings, which mark chemokines as prognostic markers and therapeutic targets for immune-modulation during chronic liver viral infection, are documented.
丙型肝炎病毒感染及其相关的肝脏炎症性疾病是一个重大的全球健康问题，影响着全球超过1.7亿人。病毒感染后，多种促炎介质促使免疫细胞募集到肝脏并引发抗病毒免疫反应。然而，当这种强烈的免疫反应未能清除病毒时，就会形成慢性感染。这反过来又导致炎症、再生和纤维化的持续过程，在许多情况下会导致肝硬化和肝细胞癌的发生。最近的多项研究表明，趋化因子及其受体是白细胞通过炎症肝脏进行再循环的关键因素。此外，趋化因子也可能参与肝脏再生、纤维化以及由炎症持续引发的恶性转化。越来越多的数据表明，不同的趋化因子和趋化因子受体可能与慢性丙型肝炎病毒感染相关肝脏疾病的不同阶段有关。多种拮抗趋化因子及其受体的小分子和肽正处于3期和2期临床试验的后期阶段。在不久的将来，这类药物有望进入临床应用，这就引发了一个问题，即它们是否可用于治疗慢性病毒感染相关的肝脏疾病。在这篇综述中，我们介绍了在理解趋化因子及其受体在慢性病毒感染相关肝脏疾病发病机制中的作用方面的最新进展。此外，还记录了这些新发现的临床意义，这些发现将趋化因子标记为慢性肝脏病毒感染期间免疫调节的预后标志物和治疗靶点。
