Parental characteristics, somatic fetal growth, and season of birth influence innate and adaptive cord blood cytokine responses

Abstract

Background: Immunologic responses at birth likely relate to subsequent risks for allergic diseases and wheezing in infancy; however, the influences of parental characteristics and prenatal factors on neonatal immune responses are incompletely understood.

Objective: This study investigates potential correlations between urban parental, prenatal, and perinatal factors on innate and adaptive stimuli-induced cytokine responses.

Methods: Five hundred sixty and 49 children of parents with and without allergic disease or asthma, respectively, were enrolled into a prospective birth cohort study (Urban Environment and Childhood Asthma). Cord blood mononuclear cells were incubated with innate and adaptive immune stimuli, and cytokine responses (ELISA) were compared with season of birth, parental characteristics, in utero stressors, and fetal growth.

Results: Many cytokine responses varied by season of birth, including 2-fold to 3-fold fluctuations with specific IFN-alpha and IFN-gamma responses. Birth weight was inversely associated with IFN-gamma responses to respiratory syncytial virus (R = -0.16), but positively associated with IL-8 responses to a variety of innate stimuli (R = 0.08-0.12). Respiratory syncytial virus-induced cytokine responses were 21% to 54% lower in children of mothers with asthma. Cytokine responses were generally lower in babies born to parents with allergy/asthma.

Conclusions: Innate cytokine responses are associated with parental allergic or airway disease, somatic fetal growth, ethnicity, and season of birth. Collectively, these findings suggest that urban prenatal exposures and familial factors affect the development of the fetal immune system.

Figures

Figure 1

Cytokine responses of cord blood cells (n = 558) to innate immune stimuli (A) and specific proteins and PHA (B). Box plots represent median values with 10th, 25th, 75th, and 90th percentiles. IL-8 responses were much higher than those for the other cytokines and are plotted on a different scale.

Figure 2

Correlation matrix for innate immune responses. Statistically significant (p

Figure 3

Correlation matrix for adaptive and PHA-induced responses. Statistically significant (p

Figure 4

Seasonal patterns of selected cytokine mean responses. A) IFN-α responses to LPS, PG, and CpG according to season (3 month intervals). B) IFN-γ responses to cockroach (CR) and dust mite (DM) extracts, and tetanus toxoid (TT). Seasonal patterns from the 4 individual study sites are depicted by the colored lines. The depicted cytokine mean responses are those with the strongest seasonality patterns (see also Figure 2). All figures demonstrate a significant quadratic effect with each panel having p