IFN-α-based treatment of patients with chronic HCV show increased levels of cells with myeloid-derived suppressor cell phenotype and of IDO and NOS

Hepatitis C virus (HCV) infection causes chronic hepatitis, which is often associated with suppressed anti-HCV immune responses. We have recently reported accumulation of myeloid-derived suppressor cells (MDSCs) and suppressed immunity in cancer patients.The main aim of this study was to determine whether chronic HCV patients harbor high of MDSCs in general and in nonresponders to IFN-based therapy in particular as well as to analyze the immune suppressive molecules.Peripheral blood samples withdrawn from 154 patients with chronic HCV infection and were categorized into responders and nonresponders based on viral titer upon IFN-α treatment.The relative and absolute numbers of MDSCs defined as Lin-/HLA-DR-/CD33+/CD11b+ increased in all HCV patients, where they were higher in nonresponders than in responders. Additionally, the levels of MDSCs after 4-6 months of treatment in responders were lower than during the course of treatment. The responders also showed higher levels of IL-2 coincided with increased numbers of dendritic cells (DCs), CD4+ and CD8+ T cells. The levels of total NOS and IDO were also higher in nonresponders as compared to responders and healthy controls, while the expression levels of CD3ζ was lower in responders as compared to nonresponders and healthy volunteers.Chronic HCV patients harbor high numbers of MDSCs, which are higher in nonresponders than in responders. The higher numbers of MDSCs associated with increases in the suppressing factors.