Adaptive cytokine production in early life differentially predicts total IgE levels and asthma through age 5 years

Background: Although it has been postulated that allergic disease is associated with a predominance of T_H2 cells, whether IgE levels and asthma might differ in their relation to early-life cytokine production is not known. Objective: We sought to assess the relationship between first-year adaptive immune cytokine production with asthma and total IgE levels through age 5 years in a nonselected birth cohort. Methods: Mitogen (concanavalin A/phorbol 12-myristate 13-acetate)-stimulated IL-4, IL-5, IL-13, and IFN-γ levels were measured in supernatants from cord blood mononuclear cells and PBMCs at birth, 3 months, and 12 months. Total serum IgE levels and physician-diagnosed active asthma were assessed at 1, 2, 3, and 5 years. Longitudinal models that adjust for both T_H1 and T_H2 cytokine production were used to determine relations of outcomes. Results: Relations of cytokines to total IgE levels and asthma were strikingly different. Total IgE levels through age 5 years were positively associated with 12-month IL-4 (P < .001), IL-5 (P < .001), and IL-13 (P = .02) levels when adjusted for IFN-γ levels and inversely associated with 12-month IFN-γ levels after IL-4 adjustment (P = .01). Active asthma through age 5 years was positively associated with 3-month IL-13 levels adjusted for IFN-γ (odds ratio, 2.6; P < .001) and inversely associated with 3-month IFN-γ levels adjusted for IL-13 (odds ratio, 0.5; P = .001). These relations were strongest for nonatopic asthma. Conclusion: Total IgE levels and active asthma through age 5 years are associated with adaptive cytokine production in early life, although relations vary temporally and with regard to the relative importance of individual cytokines.