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

J Viral Hepat. 2009 Apr;16(4):292-7. doi: 10.1111/j.1365-2893.2008.01063.x. Epub 2008 Oct 17.


North American Aboriginals have an enhanced propensity to clear HCV infection. Interferon (IFN)-alpha is a critical agent in the clearance of hepatitis C virus (HCV) and other viruses; therefore the influence of Aboriginal ethnicity on IFN-alpha responses was investigated in healthy Caucasian population control and Aboriginal cohorts. Cohort peripheral blood mononuclear cells produced similar levels of IFN-alpha upon culture with reovirus, an innocuous virus capable of triggering IFN-alpha synthesis. In addition, similar IFN-gamma synthesis was observed in the presence IFN-alpha or reovirus. In contrast, Caucasian supernatants exhibited greater IL-10 levels (P<0.005), contributing to the overall cytokine balance as assessed by IFN-gamma/IL-10 ratios being consistently elevated in the Aboriginal cohort. The potential of HCV proteins to alter IFN-alpha cytokine induction was also investigated. Although there was some indication that HCV proteins might increase IFN-alpha induced IL-10 synthesis in Caucasians and conversely, IFN-gamma synthesis in Aboriginals, the addition of HCV proteins did not influence IFN-gamma/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-alpha induced IL-10 synthesis. Supporting the differential IL-10 production, IFN-alpha 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-alpha, possibly even in the presence of viral agents. These differences could impact early immune events allowing for enhanced viral clearance in Aboriginal populations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Cell Nucleus / chemistry
  • Cytokines / biosynthesis*
  • Cytoplasm / chemistry
  • Ethnicity
  • Hepacivirus / immunology
  • Humans
  • Interferon-alpha / immunology*
  • Leukocytes, Mononuclear / immunology
  • Middle Aged
  • Reoviridae / immunology
  • STAT3 Transcription Factor / metabolism
  • Young Adult


  • Cytokines
  • Interferon-alpha
  • STAT3 Transcription Factor
  • STAT3 protein, human