Host immune players and their response to Hepatitis C therapies

Abstract

This study aimed to investigate alterations in the expression of four key cytokines (IL-7, IL-11, IL-15, and IL-27) and assess differential FAM26F expression in response to Hepatitis C virus (HCV) infection. Additionally, it sought to analyze changes in these cytokines after treatment in 244 chronic HCV patients and 28 controls undergoing various treatments, including standard interferon, pegylated interferon, and Direct Acting Antivirals (DAAs). The objective was to compare immune system regulation between treatment groups. The expression levels of FAM26F and the cytokines (IL-7, IL-11, IL-15, and IL-27) were evaluated using Real-time qPCR in PBMCs of treatment groups. Results revealed significant downregulation of IL-7 and IL-27 in infected individuals compared to healthy controls, persisting even after treatment. This suggests the crucial roles of these immune modulators in facilitating the necessary T-cell response for viral clearance. IL-11 expression also remained suppressed post-treatment, supporting viral clearance by restoring the Th1 response. The decrease in IL-11 levels during treatment indicates the restoration of the Th1 response, vital for viral clearance. IL-15, the key cytokine regulating cytotoxic cells (NKT and NK cells), displayed consistent expression across all sample groups, indicating maintained IL-15-induced cytotoxicity in both control and infected individuals. Additionally, FAM26F expression was reduced in the HCV-infected group compared to controls, but higher in HCV-recovered cases, potentially due to reduced infection and enhanced immunity. In conclusion, this research unveils the relationship between FAM26F and HCV infection, highlighting the virus’s tendency to suppress cytokine and FAM26F expression. An effective treatment strategy for establishing an ideal host immune response may involve restoring FAM26F and cytokine expression to their normal levels.