Exposure to Traffic-Related Air Pollution and Serum Inflammatory Cytokines in Children

Background: Long-term exposure to ambient air pollution can lead to adverse health effects in children; however, underlying biological mechanisms are not fully understood. Objectives: We evaluated the effect of air pollution exposure during different time periods on mRNA expression as well as circulating levels of inflammatory cytokines in children. Methods: We measured a panel of 10 inflammatory markers in peripheral blood samples from 670 8-y-old children in the Barn/Child, Allergy, Milieu, Stockholm, Epidemiology (BAMSE) birth cohort. Outdoor concentrations of nitrogen dioxide (NO2) and particulate matter (PM) with aerodynamic diameter <10μm (PM10) from road traffic were estimated for residential, daycare, and school addresses using dispersion modeling. Time-weighted average exposures during infancy and at biosampling were linked to serum cytokine levels using linear regression analysis. Furthermore, gene expression data from 16-year-olds in BAMSE (n=238) were used to evaluate links between air pollution exposure and expression of genes coding for the studied inflammatory markers. Results: A 10 μg/m3 increase of NO2 exposure during infancy was associated with a 13.6% (95% confidence interval (CI): 0.8; 28.1%) increase in interleukin-6 (IL-6) levels, as well as with a 27.8% (95% CI: 4.6, 56.2%) increase in IL-10 levels, the latter limited to children with asthma. However, no clear associations were observed for current exposure. Results were similar using PM10, which showed a high correlation with NO2. The functional analysis identified several differentially expressed genes in response to air pollution exposure during infancy, including IL10, IL13, and TNF. Conclusion: Our results indicate alterations in systemic inflammatory markers in 8-y-old children in relation to early-life exposure to traffic-related air pollution. https://doi.org/10.1289/EHP460

[1]  Christer Johansson,et al.  Can dispersion modeling of air pollution be improved by land-use regression? An example from Stockholm, Sweden , 2016, Journal of Exposure Science and Environmental Epidemiology.

[2]  Ze-Zhou Song Early-Life Exposure to Traffic-related Air Pollution and Lung Function in Adolescence. , 2016, American journal of respiratory and critical care medicine.

[3]  D. Postma,et al.  Epigenome-Wide Meta-Analysis of Methylation in Children Related to Prenatal NO2 Air Pollution Exposure , 2016, Environmental health perspectives.

[4]  Menghong Sun,et al.  Associations of potentially functional variants in IL-6, JAKs and STAT3 with gastric cancer risk in an eastern Chinese population , 2016, Oncotarget.

[5]  D. Postma,et al.  Exposure to air pollution and development of asthma and rhinoconjunctivitis throughout childhood and adolescence: a population-based birth cohort study. , 2015, The Lancet. Respiratory medicine.

[6]  G. Petkov,et al.  Proinflammatory and anti-inflammatory cytokines in adolescents from Southeast Bulgarian cities with different levels of air pollution , 2015, Toxicology and industrial health.

[7]  M. Lag,et al.  Cytokine responses induced by diesel exhaust particles are suppressed by PAR-2 silencing and antioxidant treatment, and driven by polar and non-polar soluble constituents. , 2015, Toxicology letters.

[8]  N. Mostafavi,et al.  Inflammatory markers in relation to long-term air pollution. , 2015, Environment international.

[9]  S. Vedal,et al.  Long-term Exposure to Air Pollution and Markers of Inflammation, Coagulation, and Endothelial Activation: A Repeat-measures Analysis in the Multi-Ethnic Study of Atherosclerosis (MESA) , 2015, Epidemiology.

[10]  J. Heinrich,et al.  Air pollution and cytokine responsiveness in asthmatic and non-asthmatic children. , 2015, Environmental research.

[11]  Matthew E. Ritchie,et al.  limma powers differential expression analyses for RNA-sequencing and microarray studies , 2015, Nucleic acids research.

[12]  M. Berwick,et al.  Residential Exposure to Urban Traffic Is Associated with Increased Carotid Intima-Media Thickness in Children , 2015, Journal of environmental and public health.

[13]  Qingyang Liu,et al.  Oxidative potential and inflammatory impacts of source apportioned ambient air pollution in Beijing. , 2014, Environmental science & technology.

[14]  M. Wickman,et al.  Pre- and Postnatal Exposure to Parental Smoking and Allergic Disease Through Adolescence , 2014, Pediatrics.

[15]  Susanna Esposito,et al.  Possible molecular mechanisms linking air pollution and asthma in children , 2014, BMC Pulmonary Medicine.

[16]  I. M. Velásquez,et al.  Association of interleukin 8 with myocardial infarction: results from the Stockholm Heart Epidemiology Program. , 2014, International journal of cardiology.

[17]  M. Yunesian,et al.  Long-term air pollution exposure and breast cancer , 2013 .

[18]  U. de Faire,et al.  Interaction between air pollution exposure and genes in relation to levels of inflammatory markers and risk of myocardial infarction , 2013, BMJ Open.

[19]  J. J.,et al.  Interleukin-6 via Sputum Induction as Biomarker of Inflammation for Indoor Particulate Matter among Primary School Children in Klang Valley, Malaysia , 2013, Global Journal of Health Science.

[20]  D. Strachan,et al.  Genome‐wide association study of body mass index in 23 000 individuals with and without asthma , 2013, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[21]  Bing Li,et al.  Genotoxic and inflammatory effects of organic extracts from traffic-related particulate matter in human lung epithelial A549 cells: the role of quinones. , 2013, Toxicology in vitro : an international journal published in association with BIBRA.

[22]  Hongtu Zhu,et al.  Exposure to Urban Air Pollution and Bone Health in Clinically Healthy Six-year-old Children , 2013, Arhiv za higijenu rada i toksikologiju.

[23]  Menghong Sun,et al.  Polymorphisms of the Interleukin 6 gene contribute to cervical cancer susceptibility in Eastern Chinese women , 2013, Human Genetics.

[24]  J. Pourazar,et al.  Airway inflammatory responses to diesel exhaust in allergic rhinitics , 2013, Inhalation toxicology.

[25]  A. Hofman,et al.  Air pollution, fetal and infant tobacco smoke exposure, and wheezing in preschool children: a population-based prospective birth cohort , 2012, Environmental Health.

[26]  C. Irvin,et al.  Role of IL-6 in Asthma and Other Inflammatory Pulmonary Diseases , 2012, International journal of biological sciences.

[27]  Marco A Garcia,et al.  Secondhand smoke in combination with ambient air pollution exposure is associated with increasedx CpG methylation and decreased expression of IFN-γ in T effector cells and Foxp3 in T regulatory cells in children , 2012, Clinical Epigenetics.

[28]  F. Paccaud,et al.  Effects of particulate matter on inflammatory markers in the general adult population , 2012, Particle and Fibre Toxicology.

[29]  H. Nakane Translocation of particles deposited in the respiratory system: a systematic review and statistical analysis , 2012, Environmental Health and Preventive Medicine.

[30]  Paige E. Tolbert,et al.  Residential Proximity to a Major Roadway Is Associated with Features of Asthma Control in Children , 2012, PloS one.

[31]  M. Hernandez,et al.  The effect of environmental oxidative stress on airway inflammation , 2012, Current opinion in allergy and clinical immunology.

[32]  D. Galas,et al.  Interleukin-6 Contributes to Inflammation and Remodeling in a Model of Adenosine Mediated Lung Injury , 2011, PloS one.

[33]  Bert Brunekreef,et al.  In-Traffic Air Pollution Exposure and CC16, Blood Coagulation, and Inflammation Markers in Healthy Adults , 2011, Environmental health perspectives.

[34]  D. Jarvis,et al.  Human Genome Epidemiology ( HuGE ) Review Interactive Effects of Antioxidant Genes and Air Pollution on Respiratory Function and Airway Disease : A HuGE Review , 2011 .

[35]  M. Lag,et al.  Diesel exhaust particles induce CYP1A1 and pro-inflammatory responses via differential pathways in human bronchial epithelial cells , 2010, Particle and Fibre Toxicology.

[36]  Florence Demenais,et al.  A large-scale, consortium-based genomewide association study of asthma. , 2010, The New England journal of medicine.

[37]  Tsun-Jen Cheng,et al.  Long-term air pollution exposure and risk factors for cardiovascular diseases among the elderly in Taiwan , 2010, Occupational and Environmental Medicine.

[38]  A. Peters,et al.  Particulate Matter Air Pollution and Cardiovascular Disease: An Update to the Scientific Statement From the American Heart Association , 2010, Circulation.

[39]  Michael Brauer,et al.  Effect of Early Life Exposure to Air Pollution on Development of Childhood Asthma , 2009, Environmental health perspectives.

[40]  J. Schwartz,et al.  Baseline Repeated Measures from Controlled Human Exposure Studies: Associations between Ambient Air Pollution Exposure and the Systemic Inflammatory Biomarkers IL-6 and Fibrinogen , 2009, Environmental health perspectives.

[41]  U. de Faire,et al.  Associations of long- and short-term air pollution exposure with markers of inflammation and coagulation in a population sample , 2009, Occupational and Environmental Medicine.

[42]  Zlatka Georgieva Dobreva,et al.  The inhibition of JNK and p38 MAPKs downregulates IL-10 and differentially affects c-Jun gene expression in human monocytes , 2009, Immunopharmacology and immunotoxicology.

[43]  Klaus Mann,et al.  Chronic Residential Exposure to Particulate Matter Air Pollution and Systemic Inflammatory Markers , 2009, Environmental health perspectives.

[44]  A. Peters,et al.  Modification of the Interleukin-6 Response to Air Pollution by Interleukin-6 and Fibrinogen Polymorphisms , 2009, Environmental health perspectives.

[45]  Tony Bush,et al.  Chronic Exposure to Outdoor Air Pollution and Markers of Systemic Inflammation , 2009, Epidemiology.

[46]  R. Maronpot,et al.  Immunotoxicity and Environment: Immunodysregulation and Systemic Inflammation in Children , 2009, Toxicologic pathology.

[47]  P. Vinzents,et al.  Exposure to ambient concentrations of particulate air pollution does not influence vascular function or inflammatory pathways in young healthy individuals , 2008, Particle and Fibre Toxicology.

[48]  A. Peters,et al.  Air Pollution and Inflammation (Interleukin-6, C-Reactive Protein, Fibrinogen) in Myocardial Infarction Survivors , 2007, Environmental health perspectives.

[49]  T. Kishimoto,et al.  Interleukin-6 : discovery of a pleiotropic cytokine , 2022 .

[50]  T. Sandström,et al.  Airway antioxidant and inflammatory responses to diesel exhaust exposure in healthy humans , 2006, European Respiratory Journal.

[51]  J. Kongerud,et al.  Nasal Responses in Asthmatic and Nonasthmatic Subjects Following Exposure to Diesel Exhaust Particles , 2006, Inhalation toxicology.

[52]  H. Kwon,et al.  Asthma Attack Associated with Oxidative Stress by Exposure to ETS and PAH , 2005, The Journal of asthma : official journal of the Association for the Care of Asthma.

[53]  M. Wickman,et al.  The BAMSE Project: presentation of a prospective longitudinal birth cohort study , 2002, Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology.

[54]  Yoshinobu Saito,et al.  LONG-TERM INHALATION OF DIESEL EXHAUST AFFECTS CYTOKINE EXPRESSION IN MURINE LUNG TISSUES: COMPARISON BETWEEN LOW- AND HIGH-DOSE DIESEL EXHAUST EXPOSURE , 2002, Experimental lung research.

[55]  F. Chung,et al.  Anti-inflammatory cytokines in asthma and allergy: interleukin-10, interleukin-12, interferon-gamma. , 2001, Mediators of inflammation.

[56]  M. Wickman,et al.  Traffic-related air pollution and development of allergic sensitization in children during the first 8 years of life. , 2012, The Journal of allergy and clinical immunology.

[57]  E. Wouters,et al.  Systemic and local inflammation in asthma and chronic obstructive pulmonary disease: is there a connection? , 2009, Proceedings of the American Thoracic Society.

[58]  M. Wickman,et al.  Traffic-Related Air Pollution and Childhood Respiratory Symptoms, Function and Allergies , 2008 .

[59]  C. Johansson,et al.  Exposure COMPARISON BETWEEN MEASUREMENTS AND CALCULATIONS BASED ON DISPERSION MODELLING ( EXPOSE ) , 2007 .

[60]  G. Duménil,et al.  Genotoxic and inflammatory effects of depleted uranium particles inhaled by rats. , 2006, Toxicological sciences : an official journal of the Society of Toxicology.