The influence of North American Aboriginal ethnicity on pro-inflammatory and anti-inflammatory cytokine responses to IFN-alpha

Summary. North American Aboriginals have an enhanced propensity to clear HCV infection. Interferon (IFN)-α is a critical agent in the clearance of hepatitis C virus (HCV) and other viruses; therefore the influence of Aboriginal ethnicity on IFN-α responses was investigated in healthy Caucasian population control and Aboriginal cohorts. Cohort peripheral blood mononuclear cells produced similar levels of IFN-α upon culture with reovirus, an innocuous virus capable of triggering IFN-α synthesis. In addition, similar IFN-γ synthesis was observed in the presence IFN-α or reovirus. In contrast, Caucasian supernatants exhibited greater IL-10 levels (P < 0.005), contributing to the overall cytokine balance as assessed by IFN-γ/IL-10 ratios being consistently elevated in the Aboriginal cohort. The potential of HCV proteins to alter IFN-α cytokine induction was also investigated. Although there was some indication that HCV proteins might increase IFN-α induced IL-10 synthesis in Caucasians and conversely, IFN-γ synthesis in Aboriginals, the addition of HCV proteins did not influence IFN-γ/IL-10 ratios. Finally, signal transducer and activator of transcription (STAT) 3 nuclear translocation was examined by western blot because it is a required intermediate in IFN-α induced IL-10 synthesis. Supporting the differential IL-10 production, IFN-α and core synergistically enhanced STAT3 nuclear translocation in Caucasian (P < 0.05); whereas, nuclear translocation of STAT3 remained unchanged in Aboriginal cells. Taken together, these findings suggest that ethnicity may influence certain responses to IFN-α, possibly even in the presence of viral agents. These differences could impact early immune events allowing for enhanced viral clearance in Aboriginal populations.