Role of Serum Chemokines as Inflammatory Mediators in Chronic Hepatitis C Virus Infection with Different Stages of Cirrhosis
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- Category: Vol. 80, March 2012
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Role of Serum Chemokines as Inflammatory Mediators in Chronic Hepatitis C Virus Infection with Different Stages of Cirrhosis,NIHAD A. EL-NASHAR
Abstract
Hepatitis C virus (HCV) is a leading cause of chronic liver diseases that can progress to cirrhosis. Chemokines are chemotactic mediators that are implicated in viral hepa-titis. The predominant chemokine receptor expressed in the liver is CXCR 3, suggesting that its specific ligands are important in the progression of chronic liver diseases. Also, the HCV-non-structural (NS) 5A protein of HCV (HCV NS5A protein) induces the CXC chemokine interleukin 8 (IL-8). Expression and affinity to IL-8 is different in the two receptors (CXCR 1>CXCR 2) that inhibit the antiviral actions of IFN. So, we analyzed the serum concentrations of the CXCR 3 ligand CXCL 10 (interferon-g-inducible protein 10) and CXCR 1 and CXCR 2 ligand interleukin 8 using ELISA technique in 30 patients with chronic viral hepatitis C with different stages of cirrhosis (19 males & 11 females, their mean ages were 64.50±6.60 years) compared to 20 healthy volunteers (10 males and 10 females with mean age 59.87±9.56 years) serving as controls. Serum chemokines, CXCL 10 and IL-8 were significantly increased in patients with HCV than controls (p<0.0001). Patients with established liver cirrhosis displayed significantly higher CXCL 10 and IL-8 levels than HCV infected patients without cirrhosis (p<0.0001). Highest CXCL 10 and IL-8 concentra-tions were found in patients with decompensated, Child C-staged liver cirrhosis. There were significant positive corre-lations between both of CXCL 10 and IL-8 and each of AST, ALT and gGTP and significant negative correlation with serum albumin. Moreover, CXCL 10 showed significant positive correlation with gglobulin and IL-8. However, IL-8 revealed significant positive correlations with ALP and total bilirubin.
In Conclusion, the CXCL 10 and IL-8 chemokines are the most significantly expressed chemokines in chronic hepatitis C and most likely play a role in positioning T cells in the liver. Moreover, therapeutic agents that block chemok-ine receptors, thereby decreasing inflammation, may be evaluated in humans. Additional information about chemok-ines and their receptors might also be considered as potential therapeutic targets in HCV infection.