Oddy WH, Halonen M, Martinez FD, et al. J Allergy Clin Immunol. 2003;112:723–728
Purpose of the Study.
To determine whether the cytokines in breast milk could account for some of the apparent protective effects of breastfeeding against wheeze in the first 1 year of life.
Mothers and their infants participating in the Infant Immune Study in Tucson, Arizona, were studied.
Data on breastfeeding and infant wheeze, from birth to 1 year, were collected prospectively from 243 mothers. Breast milk samples obtained at a mean postpartum age of 11 days were assayed, with enzyme-linked immunosorbent assays, for concentrations of transforming growth factor-β1 (TGF-β1), interleukin-10, tumor necrosis factor-α, and the soluble form of CD14. The dose of each cytokine was assessed for a relationship with wheeze, in bivariate and logistic regression analyses.
Greater duration of breastfeeding was significantly associated with decreased prevalence of wheeze (P = .039). There was wide variability in the levels of each cytokine in milk, as well as variability among women in the amount of each cytokine produced. There was a significant inverse association between the dose of TGF-β1 received through milk and the incidence of wheeze (P = .017); the relationship was linear (P = .006). None of the other cytokines showed a linear relationship with wheeze. In multivariate analyses, the risk of wheeze was significantly decreased (odds ratio: 0.22; 95% confidence interval: 0.05–0.89; P = .034) with increasing TGF-β1 dose (long breastfeeding and medium/high TGF-β1 level, compared with short breastfeeding and low TGF-β level).
This analysis shows that the dose of TGF-β1 received from milk has a significant relationship with infant wheeze, which might account for at least some of the protective effects of breastfeeding against wheeze.
It was previously shown that longer duration of breastfeeding was associated with reduced wheeze in both developing and industrialized countries, but it was unclear which components of breast milk conferred this protective effect. Cytokines secreted in human milk might play important roles in newborn health and in the development of infant immune responses. TGF-β1 has a potent immunosuppressive effect in the gut and acts with interleukin-10 to promote specific immunoglobulin A production, which might reduce susceptibility to both enteric and respiratory infections. A second mechanism might involve effects on infant lung development, because TGF-β1 appears to regulate the signaling mechanisms of proliferation and differentiation of lung cells in mice. More importantly, a single human study found a correlation between breastfeeding and lung function among 124 infants who underwent pulmonary function testing before 6 months of age.