title: The influence of North American Aboriginal ethnicity on pro-inflammatory and anti-inflammatory cytokine responses to IFN-alpha.
abstract: 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.
authors.affiliation: Section of Hepatology, Department of Internal Medicine, University of Manitoba, Winnepeg, MB, Canada. jdrempel@cc.umanitoba.ca
authors.forename: J D
authors.initials: JD
authors.lastname: Rempel
authors.forename: K B
authors.initials: KB
authors.lastname: Aborsangaya
authors.forename: M P
authors.initials: MP
authors.lastname: Alphonse
authors.forename: G Y
authors.initials: GY
authors.lastname: Minuk
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002467:Cell Nucleus / Q000737:chemistry; D016207:Cytokines / Q000096:biosynthesis*; D003593:Cytoplasm / Q000737:chemistry; D005006:Ethnicity; D016174:Hepacivirus / Q000276:immunology; D006801:Humans; D016898:Interferon-alpha / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008875:Middle Aged; D012087:Reoviridae / Q000276:immunology; D050796:STAT3 Transcription Factor / Q000378:metabolism; D055815:Young Adult
chemical_list: D016207:Cytokines; D016898:Interferon-alpha; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human