Ozone Inhalation Provokes Glucocorticoid-Dependent and -Independent Effects on Inflammatory and Metabolic Pathways.

Growing evidence implicates air pollutants in adverse health effects beyond respiratory and cardiovascular disease, including metabolic impacts (diabetes, metabolic syndrome, obesity) and neurological/neurobehavioral outcomes (neurodegenerative disease, cognitive decline, perceived stress, depression, suicide). We have shown that inhalation of particulate matter or ozone activates the hypothalamic-pituitary-adrenal axis in rats and increases plasma levels of the glucocorticoid corticosterone. To investigate the role of corticosterone in mediating inflammatory and metabolic effects of pollutant exposure, in this study male Fischer-344 rats were administered the 11ß-hydroxylase inhibitor metyrapone (0, 50, 150 mg/kg body weight) and exposed by nose-only inhalation for 4 h to air or 0.8 ppm ozone. Ozone inhalation provoked a 2-fold increase in plasma corticosterone, an effect blocked by metyrapone, but did not alter epinephrine levels. Inhibition of corticosterone production was associated with increased inflammatory signaling in the lungs and plasma in response to ozone, consistent with a role for glucocorticoids in limiting local and systemic inflammatory responses. Effects of ozone on insulin and glucagon, but not ghrelin or plasminogen activator inhibitor-1, were modified by metyrapone, revealing glucocorticoid-dependent and -independent effects on circulating metabolic and hemostatic factors. Several immunosuppressive and metabolic impacts of ozone in the lungs, heart, liver, kidney, and spleen were blocked by metyrapone and reproduced through exogenous administration of corticosterone (10 mg/kg body weight), demonstrating glucocorticoid-dependent effects in target tissues. Our results support involvement of endogenous glucocorticoids in ozone-induced inflammatory and metabolic effects, providing insight into potential biological mechanisms underlying health impacts and susceptibility.

Elevated contaminants contrasted with potential benefits of ω-3 fatty acids in wild food consumers of two remote first nations communities in northern Ontario, Canada.

Indigenous communities in Boreal environments rely on locally-harvested wild foods for sustenance. These foods provide many nutritional benefits including higher levels of polyunsaturated fatty acids (PUFAs; such as ω-3) than what is commonly found in store-bought foods. However, wild foods can be a route of exposure to dietary mercury and persistent organic pollutants (POPs) such as polychlorinated biphenyls (PCBs). Here, we show a strong association between the frequency of wild food consumption in adults (N=72) from two remote First Nations communities of Northern Ontario and environmental contaminants in blood (POPs) and hair (mercury). We observed that POPs and mercury were on average 3.5 times higher among those consuming wild foods more often, with many frequent wild food consumers exceeding Canadian and international health guidelines for PCB and mercury exposures. Contaminants in locally-harvested fish and game from these communities were sufficiently high that many participants exceeded the monthly consumption limits for methylmercury and PCBs. Those consuming more wild foods also had higher proportions of potentially beneficial ω-3 fatty acids including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). These results show that the benefits of traditional dietary choices in Boreal regions of Canada must be weighed against the inherent risks of contaminant exposure from these foods.

Dysregulation of cytokine response in Canadian First Nations communities: is there an association with persistent organic pollutant levels?

In vitro and animal studies report that some persistent organic pollutants (POPs) trigger the secretion of proinflammatory cytokines. Whether POP exposure is associated with a dysregulation of cytokine response remains to be investigated in humans. We studied the strength of association between plasma POP levels and circulating cytokines as immune activation markers. Plasma levels of fourteen POPs and thirteen cytokines were measured in 39 Caucasians from a comparator sample in Québec City (Canada) and 72 First Nations individuals from two northern communities of Ontario (Canada). Caucasians showed significantly higher levels of organochlorine insecticides (ß-HCH, p,p'-DDE and HCB) compared to First Nations. Conversely, First Nations showed higher levels of Mirex, Aroclor 1260, PCB 153, PCB 170, PCB 180 and PCB 187 compared to Caucasians. While there was no difference in cytokine levels of IL-4, IL-6, IL-10 and IL-22 between groups, First Nations had significantly greater average levels of IFNγ, IL-1ß, IL-2, IL-5, IL-8, IL-12p70, IL-17A, TNFα and TNFß levels compared to Caucasians. Among candidate predictor variables (age, body mass index, insulin resistance and POP levels), high levels of PCBs were the only predictor accounting for a small but significant effect of observed variance (∼7%) in cytokine levels. Overall, a weak but significant association is detected between persistent organochlorine pollutant exposure and elevated cytokine levels. This finding augments the already existing information that environmental pollution is related to inflammation, a common feature of several metabolic disorders that are known to be especially prevalent in Canada's remote First Nations communities.

Obesity and type 2 diabetes prevalence in adults from two remote first nations communities in northwestern ontario, Canada.

Objective. To assess the prevalence rates of obesity and type 2 diabetes in adults from two First Nations communities in northwestern Ontario, Canada. Methods. Body weight, height, and waist circumference as well as fasting and postprandial glucose levels following an oral glucose tolerance test were measured in 31 men and 41 women. Results. The mean age of the sample was 43 ± 13 y. The prevalence of obesity was 65.3% and was comparable between men and women. 90.3% of the individuals presented waist circumference levels greater than the thresholds associated with an increased risk of developing health problems. 26 of the 72 individuals (36.1%) were found to be type 2 diabetic. The prevalence of diabetes was not different between men and women. Conclusion. Using objective measurements, this study confirms that First Nations adults from remote communities of Canada continue to experience a disproportionately higher prevalence of obesity and type 2 diabetes than nonaboriginal Canadians.