Traffic-related air pollution in utero modifies cytokine responses to stimuli of umbilical cord blood cells: results from the NELA cohort

BACKGROUND AND AIM: Effects of prenatal exposure to air pollution on offspring cytokine responses to stimuli have been poorly studied. We examined the associations between in utero exposure to traffic-related air pollutants (TRAP) and cytokine responses to stimuli in newborns. METHODS: Data come from 235 participants of the NELA cohort. Inflammatory cytokines (IL-6, IFN- α, IL1-β and TNF-α), Th1-related (IFN-γ and IL-2), Th2-related (IL-4, IL-5 and IL-13), Th17-related (IL-17 and IL-23) and Treg-related IL-10 were assessed by Luminex technology in umbilical cord blood cultured with mitogens, pathogen associated with molecular patterns (PAMPs) stimuli and common allergens. In utero residential exposure to traffic-related nitrogen dioxide (NO₂), particulate matter (PM₂.₅ and PM₁₀) and ozone (O₃) was estimated using dispersion/chemical transport modelling. Multivariable linear regression models were performed. RESULTS: For every 10µg/m³ increase in prenatal exposure to NO₂, we found an increased IL-6 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 (11.6%, 95% CI: 3.8, 19.5), Peptidoglycan (PG) (12.0%, 95% CI: 4.1, 20.0) and p:IC (13.0%, 95% CI: 4.9, 21.2); and to allergens Der p 1 (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 5µg/m³ increase in PM₂.₅, 95% CI: 5.5, 32.5; and 20.2% per 10µg/m³ increase in PM₁₀, 95% CI: 6.0, 34.4). Per 10µg/m³ increase in NO₂, IFN-α 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. In utero NO₂ also induced an increased Th1-related IFN-γ response to mitogen Concanavalin A (7.5% per 10µg/m³ increase in NO₂, 95% CI: 0.1, 14.9). CONCLUSIONS: Prenatal exposure to TRAP may promote higher proinflammatory and Th1-related cytokine responses to stimuli in the offspring.