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Bisphenol A Promotes IL-4 Production by Th2 Cells

Tian X. · Takamoto M. · Sugane K.
Department of Immunology and Infectious Diseases, Institute of Organ Tansplants, Reconstructive Medicine and Tissue Engineering, Shinshu University Graduate School of Medicine, Matsumoto, Japan Int Arch Allergy Immunol 2003;132:240–247 (DOI:10.1159/000074305)


Background: It has been proposed that estrogen plays an important role in modulating the Th1/Th2 cytokine balance. From this viewpoint, chemicals with estrogenic responses were expected to possess similar immunoregulatory roles which have not been defined to date. To address this, we studied the effects of one of the estrogenic chemicals, bisphenol A (BPA), on the in vitro production of Th1 and Th2 cytokines. Methods: Mesenteric lymph node cells from Trichinella spiralis (Ts)-infected mice were incubated with serialfold dilutions of BPA under stimulation with Ts antigen. The Th2 cytokine production in the supernatant was determined by ELISA. The Th2 cytokine production by mesenteric lymph node cells from Ts-infected mice inoculated orally with BPA was compared with that of uninoculated mice infected with Ts. Results: The antigen-stimulated interleukin (IL)-4 production by Th2-dominant mesenteric lymph node cells from Ts-infected mice increased significantly by addition of 3 µM of BPA. The IL-5 production was not affected. The production of IL-4, but not that of IL-5, by splenocytes of Th2-skewed Leishmania major-infected BALB/c mice increased at concentrations of 3 and 10 µM of BPA. However, the interferon gamma production was not affected by BPA in Th1-skewed L. major-infected C57BL/6 mice. The production of IL-4 and IL-10, but not that of IL-13, markedly increased in Ts-infected mice inoculated orally with BPA. Conclusions: We demonstrated that the IL-4 production was increased both in vitro and in vivo by treatment with BPA. This suggests that BPA might cause allergic diseases by stimulating the IL-4 production by Th2 cells.


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