Maternal Cytokine Profiles during Pregnancy Predict Asthma in Children of Mothers without Asthma

Abstract

Little is known about whether maternal immune status during pregnancy influences asthma development in the child. We measured cytokine production in supernatants from mitogen-stimulated peripheral blood immune cells collected during and after pregnancy from the mothers of children enrolled in the Tucson Infant Immune Study, a nonselected birth cohort. Physician-diagnosed active asthma in children through age 9 and a history of asthma in their mothers were assessed through questionnaires. Maternal production of each of the cytokines IL-13, IL-4, IL-5, IFN-γ, IL-10, and IL-17 during pregnancy was unrelated to childhood asthma. However, IFN-γ/IL-13 and IFN-γ/IL-4 ratios during pregnancy were associated with a decreased risk of childhood asthma (n = 381; odds ratio [OR], 0.33; 95% confidence interval [CI], 0.17-0.66; P = 0.002; and n = 368; OR, 0.36; 95% CI, 0.18-0.71; P = 0.003, respectively). The inverse relations of these two ratios with childhood asthma were only evident in mothers without asthma (n = 309; OR, 0.18; 95% CI, 0.08-0.42; P = 0.00007; and n = 299; OR, 0.17; 95% CI, 0.07-0.39; P = 0.00003, respectively) and not in mothers with asthma (n = 72 and 69, respectively; P for interaction by maternal asthma = 0.036 and 0.002, respectively). Paternal cytokine ratios were unrelated to childhood asthma. Maternal cytokine ratios in mothers without asthma were unrelated to the children's skin-test reactivity, total IgE, physician-confirmed allergic rhinitis at age 5, or eczema in infancy. To our knowledge, this study provides the first evidence that cytokine profiles in pregnant mothers without asthma relate to the risk for childhood asthma, but not allergy, and suggests a process of asthma development that begins in utero and is independent of allergy.

Association of the Risk of Childhood Asthma at Age 6 With Maternal Allergic or Immune-Mediated Inflammatory Diseases: A Nationwide Population-Based Study

“…An allergic reaction triggers the imbalance of immune responses, including mast cells, eosinophils, neutrophils, and lymphocytes. During pregnancy, the maternal ratios of IFN-γ/IL-13 and IFN-γ/IL-4 are associated with a lower prevalence of childhood asthma ( 28 ). In a previous study, the increased prevalence of allergic rhinitis/conjunctivitis/asthma is associated with various IMIDs, including SLE, Sjögren's syndrome, myasthenia, vitiligo, and psoriasis ( 29 ).…”

Sex Bias in Asthma Prevalence and Pathogenesis

“…Studies looking at maternal stress during pregnancy and maternal obesity have also shown similar findings, with differences in DNA methylation depending on the mother's status (54). A study investigating maternal immune status during pregnancy found that while maternal production of IL-13, IL-4, IL-5, IFN-γ, IL-10, and IL-17 during pregnancy was unrelated to childhood asthma, the ratios of IFN-γ/IL-13 and IFN-γ/IL-4 during pregnancy were associated with a decreased risk of asthma (58). In utero and early exposures to farm and animal barns is protective against asthma even in genetically similar Amish and Hutterite populations (59).…”

Of pleiotropy and trajectories: Does the TGF-β pathway link childhood asthma and chronic obstructive pulmonary disease?

“…Interestingly, this relationship was found for pre-natal but not post-natal maternal cytokine levels, was evident in children of non-asthmatic but not asthmatic mothers, and held for maternal but not paternal cytokines. Moreover, this relationship was independent of childhood allergy (13).…”