Traffic-related air pollution in utero modifies cytokine responses to stimuli of umbilical cord blood cells: a cohort study

Abstract

Objective: To examine the associations between in utero exposure to traffic-related air pollutants (TRAP) and cytokine responses to stimuli in newborns. Methods: Luminex technology was used to assess cytokine responses in umbilical cord blood of 235 newborns of the NELA cohort. Samples were cultured with mitogens, pathogen associated with molecular patterns (PAMPs) stimuli and common environmental allergens. Dispersion/chemical transport modelling was used to estimate in utero residential exposures to traffic-related nitrogen dioxide (NO2), particulate matter (PM2.5 and PM10) and ozone (O3). Multivariable linear regression models were fitted. Results: Per 10 mu g/m3 increase of NO2, IL-6 increased in response to mitogens Concanavalin A (12.5 %, 95 % CI: 3.6, 21.4) and Phytohemagglutinin (PHA) (14.9 %, 95 % CI: 7.3, 22.5); to PAMPs Lipopolysaccharide (LPS) (11.6 %, 95 % CI: 3.8, 19.5), Peptidoglycan (PG) (12.0 %, 95 % CI: 4.1, 20.0) and pI:C (13.0 %, 95 % CI: 4.9, 21.2); and to allergens Der pT (11.6 %, 95 % CI: 3.4, 19.9) and olive extract (9.7 %, 95 % CI: 0.4, 19.0). IL-6 response to PHA also increased in relation to PM (19.0 % per 5 mu g/m3 increase in PM2.5, 95 % CI: 5.5, 32.5; and 20.2 % per 10 mu g/m3 increase in PM10, 95 % CI: 6.0, 34.4). Per 10 mu g/m3 increase of NO2, IFN-alpha responses to PHA and PG increased by 7.5 % (95 % CI: 0.6, 14.5) and 7.6 % (95 % CI: 0.1, 15.1), respectively. NO2 was also associated with an increased Th1-related IFN-gamma response to Concanavalin A (7.5 % per 10 mu g/m3 increase, 95 % CI: 0.1, 14.9) and decreased Th2-related IL-5 response to PAMPs PG (-6.7 %, 95 % CI: -12.8, -0.7) and pI:C (-7.6 %, 95 % CI: -14.2, -0.9). Conclusion: Prenatal exposure to TRAP may promote higher proinflammatory and Th1-related and lower Th2related cytokine responses to stimuli in the offspring.