title: Effects of gender, cytokine gene polymorphisms and environmental factors on inflammatory responses.
abstract: Previous studies have indicated that cytokine gene polymorphisms of Indigenous Australians were predominantly associated with strong pro-inflammatory responses. We tested the hypothesis that cells of donors with genetic profiles of inflammatory cytokine single nucleotide polymorphisms (SNPs) similar to Indigenous Australians produce higher pro-inflammatory responses. PBMCs from 14 donors with genetic profiles for a high risk of strong pro-inflammatory responses and 14 with low-risk profiles were stimulated with endotoxin and effects of gender, IFN-γ, cigarette smoke extract (CSE) and testosterone on cytokine responses analysed. Cytokines were calculated from standard curves (Luminex 2.3 software). No significant differences were associated with SNP profile alone. Lower pro-inflammatory responses were observed for cells from males with low- or high-risk profiles. For cells from females with high-risk profiles, anti-inflammatory IL-10 responses were significantly reduced. There was no effect of testosterone levels on responses from males. For females, results from IFN-γ-treated cells showed positive correlations between testosterone levels and IL-1β responses to endotoxin for both risk groups and TNF-α for the high-risk group. If interactions observed among CSE, IFN-γ, genetic background and testosterone reflect those in vivo, these might contribute to increased incidences of hospitalisations for infectious diseases among Indigenous women.
authors.affiliation: School of Biomedical Sciences and Pharmacy, Faculty of Health, University of Newcastle, Newcastle, Australia Hunter Medical Research Institute, Newcastle, Australia s_moscovis@hotmail.com.
authors.forename: Sophia M
authors.initials: SM
authors.lastname: Moscovis
authors.affiliation: Griffith Health Institute, Molecular Basis of Disease, and School of Medical Science, Griffith University, Southport, Australia.
authors.forename: Amanda
authors.initials: A
authors.lastname: Cox
authors.affiliation: School of Biomedical Sciences and Pharmacy, Faculty of Health, University of Newcastle, Newcastle, Australia Hunter Medical Research Institute, Newcastle, Australia.
authors.forename: Sharron T
authors.initials: ST
authors.lastname: Hall
authors.affiliation: School of Biomedical Sciences and Pharmacy, Faculty of Health, University of Newcastle, Newcastle, Australia Hunter Medical Research Institute, Newcastle, Australia.
authors.forename: Christine J
authors.initials: CJ
authors.lastname: Burns
authors.affiliation: School of Biomedical Sciences and Pharmacy, Faculty of Health, University of Newcastle, Newcastle, Australia Hunter Medical Research Institute, Newcastle, Australia.
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Scott
authors.affiliation: School of Biomedical Sciences and Pharmacy, Faculty of Health, University of Newcastle, Newcastle, Australia Hunter Medical Research Institute, Newcastle, Australia.
authors.forename: C Caroline
authors.initials: CC
authors.lastname: Blackwell
mesh_terms: D000328:Adult; D016207:Cytokines / Q000235:genetics*; D004731:Endotoxins / Q000494:pharmacology; D004777:Environment; D005260:Female; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000473:pathology*; D007371:Interferon-gamma / Q000494:pharmacology; D016753:Interleukin-10 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012306:Risk; D018570:Risk Assessment; D012727:Sex Characteristics; D012906:Smoke; D013739:Testosterone / Q000097:blood; D014026:Nicotiana / Q000737:chemistry / Q000633:toxicity; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D016207:Cytokines; D004731:Endotoxins; D012906:Smoke; D014028:Tobacco Smoke Pollution; D016753:Interleukin-10; D013739:Testosterone; D007371:Interferon-gamma
keywords: Cytokines; Indigenous Australians; cigarette smoke; endotoxin; gender; gene polymorphisms; interferon-γ