Relationship between sex hormones and RIG-I signaling in peripheral blood mononuclear cells of patients infected with hepatitis C virus

It has previously been suggested that men and women demonstrate differing immune responses to hepatitis C virus (HCV) infection, resulting in the investigation of the role of sex hormones and if they influence the anti-HCV response. The present study aimed to examine if hormone levels were associated with interferon (IFN) signaling pathways in peripheral blood mononuclear cells of 131 patients infected with HCV and 113 healthy controls. HCV infection was diagnosed based on the presence of anti-HCV antibodies and HCV RNA in serum. Expression of testosterone and estrogen was measured at the protein level using a competitive chemiluminescence immunoassay, and at the mRNA level using reverse transcription-quantitative polymerase chain reaction. HCV-infected males had increased levels of estrogen and a decreased ratio of testosterone to estrogen compared with healthy male controls (all P<0.001). HCV-infected patients demonstrated a significantly decreased expression of IFN and retinoic acid-induced gene protein I (RIG-I), RIG-I mRNA compared with controls. Pearson correlation analysis revealed that among males, levels of RIG-I correlated with levels of IFN-beta mRNA (r=0.460), testosterone (r=-0.500), and the ratio of testosterone to estrogen (r=-0.477; all P<0.001). However, levels of RIG-I did not correlate with levels of IFN-alpha mRNA (r=0.158) or estrogen (r=0.173; both P>0.05). These results suggested that testosterone or the ratio of testosterone to estrogen may inhibit RIG-I signaling and thereby influence immune responses to HCV infection.