Association Between Antenatal Cytokine Production and the Development of Atopy and Asthma at Age 6 Years

Abstract

There is mounting evidence that antenatal factors could be important in children who develop atopy and asthma. Immunologic processes appear to operate in early infancy when challenged by exposure to environmental allergens. One possible mechanism is an alteration in cytokines, which are produced in the placenta throughout gestation and serve to protect the placenta by controlling local immunologic events. The investigators measured levels of several cytokines in cord blood in a prospective birth cohort of 407 children. They included interleukins 4, 5, 6, 10, 12, and 13; interferon-␥; and tumor necrosis factor-alpha (TNF␣). At age 6 years, 34% of the study group had been diagnosed with asthma, 21% currently had asthma, and 40% had 1 or more positive skin-prick tests. The most commonly detected cytokines were interleukins 4 (73%), 6 (69%), and 13 (46%) of cord blood samples, and interferon-␥ (37%). Higher levels of interleukins 6 and 10 were associated with perinatal stress as reflected by the need for assisted delivery and lower Apgar scores. There was, however, no relationship between cytokine levels and pregnancy complications that could correlate with chronic fetal stress. Maternal smoking during pregnancy correlated with lower cord blood levels of interleukin 4 and interferon-␥, and also with a higher risk of wheezing at age 6. Higher concentrations of interferon 4, interferon-␥, and TNF␣ were related to a lower risk of physician-diagnosed asthma and atopy at age 6 years. This study provides evidence of attenuated production of cytokines characteristic of peripheral blood T cells in infants at risk of asthma and atopy. The genetic factors determining the expression of peripheral blood T cells in atopic children could also control cytokine production by placental trophoblasts. In addition, cytokine production could be sensitive to adverse environmental exposures such as maternal smoking during pregnancy.

Birth by cesarean section, allergic rhinitis, and allergic sensitization among children with a parental history of atopy

“…Such mechanisms may include reduced or absent labor in children born by cesarean section and non-passage through the birth canal during birth. Labor has been associated with alteration of neonatal immune responses (e.g., reduced lymphocytes and CD4+ helper T cells, and increased IL-6) 49,50 . In rodents, oral exposure to lipopolysaccharide during vaginal birth triggers activation of gut epithelial cells 51 .…”

Fetal Cord Blood: Aspects of Heightened Immune Responses

“…Specifically, the two cytokines IFN-γ and IL-13, which we analyzed in this study, are of interest. Production of IFN-γ (Th1 cytokine) in unstimulated CBMC was associated with a lower risk of atopic diseases in childhood (11). As a critical Th2 cytokine, IL-13 secretion is increased in the mucosa of atopic and non-atopic asthmatics compared with non-asthmatic controls (12).…”

Modulation of the Induction of Lung and Airway Allergy in the Offspring of IFN-γ-Treated Mother Mice

“…Recent studies have highlighted the possible influence of the in utero environment and fetal/maternal interactions on the development of atopy and asthma (4 -6). Macaubas et al (7) showed the relevance of immunological processes during early infancy, when the immature immune system is first directly exposed to environmental allergens, for the establishment of long-term patterns of responsiveness. They demonstrated that the prenatal cytokine environment, within which T cells develop, determines the degree of immune competence at birth and during early infancy.…”