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The influence of North American Aboriginal ethnicity on pro‐inflammatory and anti‐inflammatory cytokine responses to IFN‐alpha
Author(s) -
Rempel J. D.,
Aborsangaya K. B.,
Alphonse M. P.,
Minuk G. Y.
Publication year - 2009
Publication title -
journal of viral hepatitis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 100
eISSN - 1365-2893
pISSN - 1352-0504
DOI - 10.1111/j.1365-2893.2008.01063.x
Subject(s) - ethnic group , cytokine , medicine , immunology , alpha (finance) , sociology , anthropology , clinical psychology , construct validity , psychometrics
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.