Prenatal Exposure to Di-Ethyl Phthalate (DEP) Is Related to Increasing Neonatal IgE Levels and the Altering of the Immune Polarization of Helper-T Cells

Abstract

Introduction: Phthalates are substances that are added to plastic products to increase their plasticity. These substances are released easily into the environment and can act as endocrine disruptors. Epidemiological studies in children have showed inconsistent findings regarding the relationship between prenatal or postnatal exposure to phthalates and the risk of allergic disease. Our hypothesis is that prenatal exposure to phthalates may contribute to the development of allergies in children. Material and methods: The objective of this study was to determine the associations between urinary phthalate metabolite concentrations in pregnant women, maternal atopic diathesis, maternal lifestyle, and cord blood IgE. Pregnant mothers and paired newborns (n = 101) were enrolled from an antenatal clinic. The epidemiologic data and the clinical information were collected using standard questionnaires and medical records. The maternal blood and urine samples were collected at 24–28 weeks gestation, and cord blood IgE, IL-12p70, IL-4, and IL-10 levels were determined from the newborns at birth. The link between phthalates and maternal IgE was also assessed. To investigate the effects of phthalates on neonatal immunity, cord blood mononuclear cells (MNCs) were used for cytokine induction in another in vitro experiment. Results: We found that maternal urine monoethyl phthalate (MEP) (a metabolite of di-ethyl phthalate (DEP)) concentrations are positively correlated with the cord blood IgE of the corresponding newborns. The cord blood IL-12p70 levels of mothers with higher maternal urine MEP groups (high DEP exposure) were lower than mothers with low DEP exposure. In vitro experiments demonstrated that DEP could enhance IL-4 production of cord blood MNCs rather than adult MNCs. Conclusion: Prenatal DEP exposure is related to neonatal IgE level and alternation of cytokines relevant to Th1/Th2 polarization. This suggests the existence of a link between prenatal exposure to specific plasticizers and the future development of allergies.

Age-related differences in IgE between childhood and adulthood allergic asthma: Analysis of NHANES 2005–2006

“…Specifically, phthalates are used as plasticizers in various industries and have become ubiquitous pollutants in air and dust. 34 The association between phthalates and allergic diseases as well as IgE has been reported in several studies, 35 , 36 , 37 and its possible mechanism is that phthalate exposure could disrupt the balance of innate and adaptive immunity and produce epigenetic modifications. 38 , 39 , 40 On the other hand, PAHs are classified as atmospheric particulate matter (PM 2.5), and their effects on IgE have already been reported; that is, they can enhance B-cell differentiation in an isotype-specific way and promote IgE production, 41 , 42 which mainly occurs in younger age groups.…”

Sex-Specific Associations between Prenatal Exposure to Di(2-ethylhexyl) Phthalate, Epigenetic Age Acceleration, and Susceptibility to Early Childhood Upper Respiratory Infections

“…However, the MIREC study found that maternal urinary mono(3carboxypropyl) phthalate (MCPP) concentrations during pregnancy were associated with increased levels of IgE and interleukin-33 (IL-33)/ thymic stromal lymphopoietin (TSLP) in their overall, but not their sex-stratified, analyses [32]. Similarly, other phthalates (e.g., di-n-butyl phthalate (DnBP), molar sum of dibutyl phthalates (DBPs), and benzyl butyl phthalate (BBzP)) have been linked to altered immune cell (e.g., cytokines, chemokines) profiles in cord blood [33,34]. These altered immune profiles are likely related to infection susceptibility [33] and are thought to explain the role of prenatal exposure to phthalates in the etiology of childhood atopy [32,63].…”

“…Similarly, other phthalates (e.g., di-n-butyl phthalate (DnBP), molar sum of dibutyl phthalates (DBPs), and benzyl butyl phthalate (BBzP)) have been linked to altered immune cell (e.g., cytokines, chemokines) profiles in cord blood [33,34]. These altered immune profiles are likely related to infection susceptibility [33] and are thought to explain the role of prenatal exposure to phthalates in the etiology of childhood atopy [32,63]. Although the current examination of prenatal DEHP exposure and childhood colds (i.e., a measure related to immune health) is not directly comparable to these other examinations of immunological profiles, this evidence cumulatively suggests that prenatal phthalate exposure may have immunotoxic effects.…”

“…Several studies have examined prenatal exposure to DEHP and early immune system function in humans. In studies investigating prenatal exposure to phthalates and immune system indices in umbilical cord blood, prenatal DEHP was not associated with elevated immune biomarkers (i.e., IgE, thymic stromal lymphopoietin (TSL), interleukin-33 (IL-33)) [32,33] or altered immune cell profiles (e.g., cytokines, chemokines) [34]. Further, little is known about the potential effects of prenatal DEHP exposure on childhood susceptibility to respiratory illnesses.…”

Environmental Health and Toxicology: Immunomodulation Promoted by Endocrine-Disrupting Chemical Tributyltin

“…Similar effects have already been observed for TBT in C57BL/6 mice models [ 76 , 77 , 109 ]. Furthermore, increased levels of IL-4 and decreased levels of IL-12 were observed in the umbilical cord blood of newborns whose mothers had higher amounts of monoethyl phthalate (MEP), a metabolite of di-ethyl phthalate (DEP), in blood and urine (during weeks 24 to 28 of gestation), indicating a possible polarization of newborn T cells towards the Th2 phenotype [ 110 ]. Bisphenol A (BPA) at doses of 10, 30 and 50 µM for 12 h led to a greater translocation of the transcription factor NF-κB p65 and to an increase in the production of cytokines IL-1β, IL-6 and TNF-α, together with nitric oxide and prostaglandin E2 (PGE2), in murine macrophages of the RAW264.7 lineage, suggesting that BPA can induce a pro-inflammatory response in these cells [ 111 ].…”