title: Influence of persistent organic pollutants on the complement system in a population-based human sample.
abstract: BACKGROUND
  Persistent organic pollutants (POPs) are toxic compounds generated through various industrial activities and have adverse effects on human health. Studies performed in cell cultures and animals have revealed that POPs can alter immune-system functioning. The complement system is part of innate immune system that helps to clear pathogens from the body. We performed a large-scale population-based study to find out associations between summary measures of different POPs and different complement system markers.
  
  
  METHODS
  In this cross-sectional study, 16 polychlorinated biphenyls (PCBs), 3 organochlorine (OC) pesticides, octachloro-p-dibenzodioxin, and 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) were analyzed for their association with levels of protein complement 3 (C3), 3a (C3a), 4 (C4) and C3a/C3 ratio. A total of 992 individuals (all aged 70 years, 50% females) were recruited from the Prospective Investigation of the Vasculature in Uppsala Seniors cohort. Regression analysis adjusting for a variety of confounders was performed to study the associations of different POP exposures (total toxic equivalency value or TEQ and sum of 16 PCBs) with protein complements.
  
  
  RESULTS
  The TEQ values were found to be positively associated with C3a (β=0.07, 95% CI=0.017-0.131, p=0.01) and C3a/C3 ratio (β=0.07, 95% CI=0.015-0.126, p=0.01) taking possible confounders into account. The association observed was mainly driven by PCB-126.
  
  
  CONCLUSIONS
  In this study involving 992 elderly individuals from the general population, we showed that POPs, mainly PCB-126, were associated with levels of complement system markers indicating that the association of these toxic compounds with downstream disease could be mediated by activation of immune system.
authors.affiliation: Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden. Electronic address: Jitender.Kumar@medsci.uu.se.
authors.forename: Jitender
authors.initials: J
authors.lastname: Kumar
authors.affiliation: Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University, Uppsala, Sweden.
authors.forename: P Monica
authors.initials: PM
authors.lastname: Lind
authors.affiliation: Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden.
authors.forename: Samira
authors.initials: S
authors.lastname: Salihovic
authors.affiliation: MTM Research Centre, School of Science and Technology, Örebro University, Örebro, Sweden.
authors.forename: Bert
authors.initials: B
authors.lastname: van Bavel
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden; Department of Chemistry and Biomedical Sciences, Linnaeus University, Kalmar, Sweden.
authors.forename: Kristina N
authors.initials: KN
authors.lastname: Ekdahl
authors.affiliation: Department of Chemistry and Biomedical Sciences, Linnaeus University, Kalmar, Sweden.
authors.forename: Bo
authors.initials: B
authors.lastname: Nilsson
authors.affiliation: Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Lind
authors.affiliation: Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Ingelsson
mesh_terms: D000368:Aged; D003176:Complement C3 / Q000276:immunology*; D015926:Complement C3a / Q000276:immunology*; D003430:Cross-Sectional Studies; D004147:Dioxins / Q000032:analysis / Q000633:toxicity; D004785:Environmental Pollutants / Q000032:analysis / Q000633:toxicity*; D005260:Female; D055768:Halogenated Diphenyl Ethers / Q000032:analysis / Q000633:toxicity; D006801:Humans; D006843:Hydrocarbons, Chlorinated / Q000032:analysis / Q000633:toxicity; D007107:Immune System / Q000187:drug effects*; D008297:Male; D015233:Models, Statistical; D010575:Pesticides / Q000032:analysis / Q000633:toxicity; D011078:Polychlorinated Biphenyls / Q000032:analysis / Q000633:toxicity*; D000072317:Polychlorinated Dibenzodioxins / Q000032:analysis / Q000633:toxicity; D011446:Prospective Studies; D012044:Regression Analysis; D013548:Sweden
chemical_list: D003176:Complement C3; D004147:Dioxins; D004785:Environmental Pollutants; D055768:Halogenated Diphenyl Ethers; D006843:Hydrocarbons, Chlorinated; D010575:Pesticides; D000072317:Polychlorinated Dibenzodioxins; C511295:2,2',4,4'-tetrabromodiphenyl ether; D015926:Complement C3a; D011078:Polychlorinated Biphenyls; C023035:3,4,5,3',4'-pentachlorobiphenyl
keywords: Complement system markers; Epidemiology; Persistent organic pollutants; TEQ