High plasma IL-6 levels may enhance the adverse effects of mouse allergen exposure in urban schools on asthma morbidity in children

Abstract

Background: Few data on the relationships between environmental exposures, asthma morbidity, and systemic IL-6 inflammation exist.

Objective: We sought to determine whether baseline plasma IL-6 level is associated with increased asthma morbidity in children exposed to mouse allergen in inner-city classrooms.

Methods: Data from the longitudinal School Inner-City Asthma Studies of 215 children with asthma, aged 4 to 14 years and recruited from urban elementary schools, were analyzed. Given the unknown threshold of IL-6 risk levels and skewness of the distribution, the children were stratified into tertiles as follows: low baseline IL-6 level (<0.013 pg/mL), moderate baseline IL-6 level (0.013-0.302 pg/mL), and high baseline IL-6 level (>0.302 pg/mL). Relationships between plasma IL-6 level and body mass index (BMI) percentile, inflammatory markers, lung function, mouse allergen exposure, and asthma outcomes were assessed.

Results: Cross-sectional analysis demonstrated that increasing IL-6 level was associated with higher BMI percentile (P < .0001), C-reactive protein level (P = .0006), and blood neutrophil count (P = .0024). IL-6 was not associated with type 2 inflammatory markers, including blood eosinophil count, allergic sensitization, or fractional exhaled nitric oxide level. Longitudinal analysis showed that children with high IL-6 levels had a higher number of days with asthma symptoms than did those children with moderate (incidence rate ratio = 1.74 [95% CI = 1.10-2.77]; P = .0187) or low (incidence rate ratio =1.83 [95% CI = 1.21-2.77]; P = .0043) IL-6 levels. Children with high IL-6 levels who were exposed to increasing levels of mouse allergen exhibited lower ratios of FEV₁ value to forced vital capacity than did children with moderate IL-6 levels (β = -0.0044 [95% CI = -0.0073 to -0.0015]; pairwise interaction P = .0028) or low IL-6 levels (β = -0.0042 [95% CI = - 0.0070 to -0.0013]; pairwise interaction P = .0039).

Conclusions: Inner-city children with asthma and high plasma IL-6 levels are more likely to have an increased BMI, elevated C-reactive protein level, elevated blood neutrophil count, and greater asthma symptoms. High IL-6 level appears to increase susceptibility to the effects of classroom exposure to mouse allergen on lung function in urban children.

Keywords: BMI; IL-6; allergen; asthma; body mass index; children; inner-city; metabolic dysfunction; obesity.