Immune development in urban children and its relationship to environmental exposures, allergic sensitization, and asthma

Background: Early-life environmental exposures influence the incidence of allergic diseases and asthma, possibly by modifying immune development. Exposure to selected indoor aeroallergens has been associated with reduced wheezing and childhood asthma. Objectives: We sought to determine whether allergen exposure in early life promotes immune development and reduces asthma risk. Methods: From birth through age 7, we measured cytokine responses of peripheral blood mononuclear cells from 442 children in the Urban Environment and Childhood Asthma study. We then compared allergen and endotoxin levels in house dust collected in the first 3 years to cytokine responses, atopy and longitudinal allergic sensitization trajectories, and asthma (age 7). Results: Cord blood cytokine responses had unique features but were poorly predictive of subsequent responses. Early cockroach, mouse, and cat allergen exposures were significantly associated with selected IFN-α, IL-12p40, and TNF responses to innate stimuli, mitogen-induced IFN-γ (cockroach and mouse), and dust mite–induced IFN-γ (mouse) at age 7. Early onset of aeroallergic sensitization was positively associated with allergen-induced type 2 responses that started at ages 1-3 years and intensified at ages 5-7. In logistic regression models, cytokine responses modestly predicted atopy but not asthma (AUROC 0.69 ± 0.14 and 0.57 ± 0.08, respectively). Conclusions: Associations between preschool aeroallergen exposures and cytokine responses through age 7 years suggest a possible role in modifying systemic immune development. Progressively increasing aeroallergen-induced type 2 responses were associated with early-onset allergic sensitization. In contrast, asthma at age 7 was not associated with distinct cytokine responses, perhaps reflecting the multiple inflammatory mechanisms related to early-onset childhood asthma.