Effects of gender, cytokine gene polymorphisms and environmental factors on inflammatory responses.
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.
['Moscovis|Sophia M|SM|', 'Cox|Amanda|A|', 'Hall|Sharron T|ST|', 'Burns|Christine J|CJ|', 'Scott|Rodney J|RJ|', 'Blackwell|C Caroline|CC|']
D000328:Adult D016207:Cytokines D004731:Endotoxins D004777:Environment D005260:Female D006801:Humans D007249:Inflammation D007371:Interferon-gamma D016753:Interleukin-10 D008297:Male D008875:Middle Aged D044468:Native Hawaiian or Other Pacific Islander D011110:Polymorphism, Genetic D020641:Polymorphism, Single Nucleotide D012306:Risk D018570:Risk Assessment D012727:Sex Characteristics D012906:Smoke D013739:Testosterone D014026:Tobacco D014028:Tobacco Smoke Pollution D055815:Young Adult
gender Cytokines gene polymorphisms Indigenous Australians endotoxin cigarette smoke interferon-γ