Epidemiologic data suggest a link between nursing by asthmatic mothers and increased risk of allergy in babies. We sought to experimentally test the potential contribution of breast milk mediator(s) in a mouse model of maternal transmission of asthma risk by evaluating the effect of adoptive nursing on asthma susceptibility in the offspring. We measured airway hyperresponsiveness (AHR) and allergic airway inflammation (AI) after an intentionally suboptimal OVA Ag sensitization, tested the allergen independence of the maternal effect by using a second allergen, casein, for sensitization of the baby mice, and tested the potential role of cytokines by measuring their levels in breast milk. Offspring of asthmatic, but not normal, mothers showed AHR and AI, indicating a maternal transfer of asthma risk. After adoptive nursing, both groups (litters born to asthmatic mothers and nursed by normal mothers, and normal babies nursed by asthmatic mothers) showed AHR (enhanced pause after methacholine aerosol, 50 mg/ml, 3.7 ± 0.7, 4.2 ± 0.5, respectively, vs 1.1 ± 0.1 normal controls, n = 25, p < 0.01) and AI, seen as eosinophilia on histology and bronchoalveolar lavage (40.7 ± 4.5%, 28.7 ± 3.7%, vs 1.0 ± 0.5% normals, n = 25, p < 0.01) after OVA sensitization. Similar results using casein allergen were observed. Multiplex assays for cytokines (IFN-γ, IL-2, IL-4, IL-5, TNF-α, and IL-13) in breast milk were negative. Breast milk is sufficient, but not necessary, to mediate allergen-independent maternal transmission of asthma risk to offspring.

We tested the potential of CpG oligodeoxynucleotides (ODN) to reverse the increased susceptibility to allergic airways disease in neonatal mice in a model of maternal transmission of asthma risk. Offspring of OVA-sensitized and challenged BALB/c mother mice were subjected to an intentionally suboptimal sensitization protocol that has minimal effects on normal mice, but results in airway hyperresponsiveness (AHR) and airway inflammation (AI) in babies of asthmatic mother mice. We evaluated pulmonary function and AI in CpG- or control ODN-treated offspring. CpG treatment of neonates on day 4 of life prevents the AHR otherwise seen in this model (enhanced pause at 100 mg/ml methacholine: CpG, 0.9 ± 0.1; ODN control, 3.8 ± 0.6; n = 62; p < 0.005). It also prevented the development of AI, as evident in decreased bronchoalveolar lavage eosinophilia (CpG, 1.2 ± 0.3%; ODN, 31.4 ± 4.1%; n = 56; p < 0.005), diminished the severity of AI on histopathology, and resulted in lower IL-5 levels in bronchoalveolar lavage fluid. The effect of CpG persisted for at least 4–6 wk and was allergen independent. Treatment with CpG just before OVA aerosol challenge also prevented allergic responses. The data support the potential for immunomodulatory therapy with CpG in early life to reduce susceptibility to asthma.