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 (β-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-1β, IL-2, IL-5, IL-8, IL-12p70, IL-17A, TNFα and TNFβ 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.
References
[1]
Semeena VS, Lammel G (2005) The significance of the grasshopper effect on the atmospheric distribution of persitent organic sunbstances. Geophysical Research Letters 32: 1–5.
[2]
McFarland VA, Clarke JU (1989) Environmental occurrence, abundance, and potential toxicity of polychlorinated biphenyl congeners: considerations for a congener- specific analysis. Environ Health Perspect 81: 225–239.
[3]
Vallack HW, Bakker DJ, Brandt I, Brostrom-Lunden E, Brouwer A, et al. (1998) Controlling persistent organic pollutants – what next? Environmental Toxicology and Pharmacology 6: 143–175.
[4]
Donaldson SG, Van Oostdam J, Tikhonov C, Feeley M, Armstrong B, et al. (2010) Environmental contaminants and human health in the Canadian Arctic. Science of the Total Environment 408: 5165–5234.
[5]
Barrie LA, Gregor D, Hargrave B, Lake R, Muir D, et al. (1992) Arctic Contaminants – Sources, Occurrence and Pathways. Science of the Total Environment 122: 1–74.
[6]
MacDonald RW, Barrie LA, Bidleman T, Diamond ML, Gregor DJ, et al. (2000) Contaminants in the Canadian Arctic: 5 years of progress in understanding sources, occurrence and pathways. Science and the Total Environment 254: 234.
[7]
Van Oostdam J, Donaldson SG, Feeley M, Arnold D, Ayotte P, et al. (2005) Human health implications of environmental contaminants in Arctic Canada: A review. Science of the Total Environment 351: 165–246.
[8]
Van Oostdam JC, Dewailly E, Gilman A, Hansen JC, Odland JO, et al. (2004) Circumpolar maternal blood contaminant survey, 1994–1997 organochlorine compounds. Science of the Total Environment 330: 55–70.
[9]
Sandau CD, Ayotte P, Dewailly E, Duffe J, Norstrom RJ (2002) Pentachlorophenol and Hydroxylated Polychlorinated Biphenyl Metabolites in Umbilical Cord Plasma of Neonates from Coastal Populations in Quebec. Environmental Health Perspectives 110: 411–417.
[10]
Dewailly E, Mulvad G, Pedersen HS, Ayotte P, Demers A, et al. (1999) Concentration of organochlorines in human brain, liver, and adipose tissue autopsy samples from Greenland. Environment Health and Perspectives 107: 823–828.
[11]
Neel BA, Sargis RM (2011) The paradox of progress: environmental disruption of metabolism and the diabetes epidemic. Diabetes 60: 1838–1848.
[12]
Beard J, Sladden T, Morgan G, Berry G, Brooks L, et al. (2003) Health impacts of pesticide exposure in a cohort of outdoor workers. Environ Health Perspect 111: 724–730.
[13]
Bertazzi PA, Consonni D, Bachetti S, Rubagotti M, Baccarelli A, et al. (2001) Health effects of dioxin exposure: a 20-year mortality study. Am J Epidemiol 153: 1031–1044.
[14]
Calvert GM, Sweeney MH, Deddens J, Wall DK (1999) Evaluation of diabetes mellitus, serum glucose, and thyroid function among United States workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Occup Environ Med 56: 270–276.
[15]
Henriksen GL, Ketchum NS, Michalek JE, Swaby JA (1997) Serum dioxin and diabetes mellitus in veterans of Operation Ranch Hand. Epidemiology 8: 252–258.
[16]
Turyk M, Anderson H, Knobeloch L, Imm P, Persky V (2009) Organochlorine exposure and incidence of diabetes in a cohort of Great Lakes sport fish consumers. Environ Health Perspect 117: 1076–1082.
[17]
Wang SL, Tsai PC, Yang CY, Leon Guo Y (2008) Increased risk of diabetes and polychlorinated biphenyls and dioxins: a 24-year follow-up study of the Yucheng cohort. Diabetes Care 31: 1574–1579.
[18]
Lee DH, Lee IK, Song K, Steffes M, Toscano W, et al. (2006) A strong dose-response relation between serum concentrations of persistent organic pollutants and diabetes: results from the National Health and Examination Survey 1999–2002. Diabetes Care 29: 1638–1644.
[19]
Humblet O, Birnbaum L, Rimm E, Mittleman MA, Hauser R (2008) Dioxins and cardiovascular disease mortality. Environ Health Perspect 116: 1443–1448.
[20]
Dirinck E, Jorens PG, Covaci A, Geens T, Roosens L, et al. (2011) Obesity and persistent organic pollutants: possible obesogenic effect of organochlorine pesticides and polychlorinated biphenyls. Obesity (Silver Spring) 19: 709–714.
[21]
Elobeid MA, Padilla MA, Brock DW, Ruden DM, Allison DB (2010) Endocrine disruptors and obesity: an examination of selected persistent organic pollutants in the NHANES 1999–2002 data. Int J Environ Res Public Health 7: 2988–3005.
[22]
Lee DH, Lee IK, Porta M, Steffes M, Jacobs DR Jr (2007) Relationship between serum concentrations of persistent organic pollutants and the prevalence of metabolic syndrome among non-diabetic adults: results from the National Health and Nutrition Examination Survey 1999–2002. Diabetologia 50: 1841–1851.
[23]
Lee DH, Lind L, Jacobs DR Jr, Salihovic S, van Bavel B, et al. (2011) Associations of persistent organic pollutants with abdominal obesity in the elderly: The Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Environ Int.
[24]
Porta M, Gasull M, Puigdomenech E, Gari M, Bosch de Basea M, et al. (2010) Distribution of blood concentrations of persistent organic pollutants in a representative sample of the population of Catalonia. Environ Int 36: 655–664.
[25]
First Nations Centre (2005) First Nations regional longitudinal health survey (RHS) 2002/03: the people report. In: First Nations information governance committee assembly of First Nations, editor: First Nations Centre at the national Aboriginal health organization.
[26]
Green C, Blanchard JF, Young TK, Griffith J (2003) The epidemiology of diabetes in the Manitoba-registered First Nation population: current patterns and comparative trends. Diabetes Care 26: 1993–1998.
[27]
Haman F, Fontaine-Bisson B, Batal M, Imbeault P, Blais JM, et al. (2010) Obesity and type 2 diabetes in Northern Canada's remote First Nations communities: the dietary dilemma. International Journal of Obesity 34: S24–31.
[28]
Receveur O, Kuhnlein HV (1998) Benefits of traditional food in Dene/Metis communities. Int J Circumpolar Health 57: 219–221.
[29]
Robidoux MA, Batal M, Imbeault P, Blais JM, Pal S, et al. (2012) Traditional foodways in two contemporary northern First Nations communities. Canadian Journal of Native Studies 32.
[30]
Imbeault P, Tremblay A, Simoneau JA, Joanisse DR (2002) Weight loss-induced rise in plasma pollutant is associated with reduced skeletal muscle oxidative capacity. American Journal of Physiology 282: E574–579.
[31]
Imbeault P, Haman F, Blais JM, Pal S, Seabert T, et al. (2011) Obesity and type 2 diabetes prevalence in adults from two remote First Nations communities in northwestern Ontario, Canada. J Obes 2011: 267509.
[32]
Health Canada (2003) Canadian guidelines for body weight classification in adults. In: Office of Nutrition Policy, Promotion , editors. Ottawa: Health Canada.
[33]
Imbeault P, Depault I, Haman F (2009) Cold exposure increases adiponectin levels in men. Metabolism 58: 552–559.
[34]
Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, et al. (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28: 412–419.
[35]
Rhainds M, Levallois P, Dewailly E, Ayotte P (1999) Lead, mercury, and organochlorine compound levels in cord blood in Quebec, Canada. Arch Environ Health 54: 40–47.
[36]
Safe SH (1994) Polychlorinated biphenyls (PCBs): environmental impact, biochemical and toxic responses, and implications for risk assessment. Critical Reviews in Toxicology 24: 87–149.
[37]
Macdonald RW, Harner T, Fyfe J (2005) Recent climate change in the Arctic and its impact on contaminant pathways and interpretation of temporal trend data. Sci Total Environ 342: 5–86.
[38]
Hotamisligil GS (2006) Inflammation and metabolic disorders. Nature 444: 860–867.
[39]
Hotamisligil GS, Arner P, Caro JF, Atkinson RL, Spiegelman BM (1995) Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. Journal of Clinical Investigation 95: 2409–2415.
[40]
Kern PA, Saghizadeh M, Ong JM, Bosch RJ, Deem R, et al. (1995) The expression of tumor necrosis factor in human adipose tissue. Regulation by obesity, weight loss, and relationship to lipoprotein lipase. Journal of Clinical Investigation 95: 2111–2119.
[41]
Bastard JP, Maachi M, Van Nhieu JT, Jardel C, Bruckert E, et al. (2002) Adipose tissue IL-6 content correlates with resistance to insulin activation of glucose uptake both in vivo and in vitro. J Clin Endocrinol Metab 87: 2084–2089.
[42]
Vozarova B, Weyer C, Hanson K, Tataranni PA, Bogardus C, et al. (2001) Circulating interleukin-6 in relation to adiposity, insulin action, and insulin secretion. Obes Res 9: 414–417.
[43]
Jager J, Gremeaux T, Cormont M, Le Marchand-Brustel Y, Tanti JF (2007) Interleukin-1beta-induced insulin resistance in adipocytes through down-regulation of insulin receptor substrate-1 expression. Endocrinology 148: 241–251.
[44]
Vandanmagsar B, Youm YH, Ravussin A, Galgani JE, Stadler K, et al. (2011) The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance. Nat Med 17: 179–188.
[45]
Oades RD, Myint AM, Dauvermann MR, Schimmelmann BG, Schwarz MJ (2010) Attention-deficit hyperactivity disorder (ADHD) and glial integrity: an exploration of associations of cytokines and kynurenine metabolites with symptoms and attention. Behav Brain Funct 6: 32.
[46]
El-Ansary AK, Ben Bacha AG, Al-Ayadhi LY (2011) Proinflammatory and proapoptotic markers in relation to mono and di-cations in plasma of autistic patients from Saudi Arabia. J Neuroinflammation 8: 142.
[47]
Cowan J, Pandey S, Filion LG, Angel JB, Kumar A, et al. (2012) Comparison of interferon-gamma-, interleukin (IL)-17- and IL-22-expressing CD4 T cells, IL-22-expressing granulocytes and proinflammatory cytokines during latent and active tuberculosis infection. Clin Exp Immunol 167: 317–329.
[48]
Hennig B, Meerarani P, Slim R, Toborek M, Daugherty A, et al. (2002) Proinflammatory properties of coplanar PCBs: in vitro and in vivo evidence. Toxicol Appl Pharmacol 181: 174–183.
[49]
Arsenescu V, Arsenescu RI, King V, Swanson H, Cassis LA (2008) Polychlorinated biphenyl-77 induces adipocyte differentiation and proinflammatory adipokines and promotes obesity and atherosclerosis. Environ Health Perspect 116: 761–768.
[50]
Reading J (2009) The crisis of chronic disease among Aboriginal peoples: a challenge for public health, population health and social policy. Victoria, British Columbia, Canada: Centre for Aboriginal Health Research.
