Exposure to Bisphenol A prenatally or in adulthood promotes T(H)2 cytokine production associated with reduction of CD4CD25 regulatory T cells.
BACKGROUND
Bisphenol A (BPA) is a widespread endocrine-disrupting chemical that can affect humans and animals.


OBJECTIVE
We investigated the effects of adult or prenatal exposure to BPA on T-helper (T(H))1/T(H)2 immune responses and the mechanisms underlying these effects.


METHODS
To evaluate the effects of exposure to BPA in adulthood, male Leishmania major-susceptible BALB/c and -resistant C57BL/6 mice were subcutaneously injected with 0.625, 1.25, 2.5, and 5 micromol BPA 1 week before being infected with L. major. To evaluate prenatal exposure, female mice were given BPA-containing drinking water at concentrations of 1, 10, and 100 nM for 2 weeks, then mated, and given BPA for another week. Male 10-week-old offspring were infected with L. major. Footpad swelling was assessed as a measure of the course of infection.


RESULTS
Mice exposed to BPA prenatally or in adulthood showed a dose-dependent increase in footpad swelling after being infected with L. major. Exposure to BPA in adulthood significantly promoted antigen-stimulated production of interleukin (IL)-4, IL-10, and IL-13 but not interferon-gamma (IFN-gamma). However, mice prenatally exposed to BPA showed increased production of not only IL-4 but also IFN-gamma. The percentages of CD4(+)CD25(+) cells were decreased in mice exposed to BPA either prenatally or in adulthood. Effects of prenatal BPA exposure were far more pronounced than effects of exposure in adulthood.


CONCLUSIONS
BPA promotes the development of T(H)2 cells in adulthood and both T(H)1 and T(H)2 cells in prenatal stages by reducing the number of regulatory T cells.
Yan
Huimin
H
Department of Infection and Host Defense, Division of Immunology and Infectious Diseases, Shinshu University Graduate School of Medicine, Matsumoto, Japan.
Takamoto
Masaya
M
Sugane
Kazuo
K
D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D001559:Benzhydryl Compounds; D015704:CD4 Antigens / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D018320:Leishmania major; D016773:Leishmaniasis, Cutaneous / Q000276:immunology; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010636:Phenols / Q000633:toxicity*; D011247:Pregnancy; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000187:drug effects*; D018417:Th1 Cells / Q000166:cytology / Q000187:drug effects; D018418:Th2 Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000098826:Bisphenol A Compounds
D000393:Air Pollutants; D001559:Benzhydryl Compounds; D015704:CD4 Antigens; D016207:Cytokines; D007371:Interferon-gamma; D053645:Interleukin-2 Receptor alpha Subunit; D007378:Interleukins; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds