Studies on the effect of endocrine disrupters on autoimmune disease and its mechanisms

本研究旨在探讨双酚A（BPA）等内分泌干扰物对胶原诱导性关节炎（CIA）小鼠的影响。通过将用完全弗氏佐剂乳化的II型胶原（CII）皮下注射到尾根部（第0天），随后在第21天加强注射来诱导CIA。从第0天到第42天，每天口服不同剂量的BPA。测量脾淋巴细胞分泌的抗-CII IgG 2a抗体和IFN-γ作为Th 1免疫应答的指标，而抗-CII IgG 1抗体和IL-4作为Th 2应答的指标。结果表明，BPA的管理增加了CIA的发病率和严重程度。疾病的增强与抗CII IgG和IgG 2a抗体的显著产生相关。DEP治疗也增强了脾细胞对CII的增殖反应。在暴露于BPA的小鼠中，Thl和Th 2免疫应答均显著增强，尽管Thl应答的增强似乎大于Th 2应答的增强。在暴露于雌二醇的小鼠中也观察到这些免疫反应的增强。这些结果表明，暴露于BPA可能会影响自身免疫性疾病。

The present study was undertaken to investigate the effect of endocrine disrupters including bisphenol A (BPA) on collagen-induced arthritis (CIA) in mice which is an experimental model of autoimmune disease. CIA was induced by subcutaneous injection of type II collagen (CII) emulsified with complete Freund's adjuvant into the base of the tail (day 0) followed by a booster injection on day 21. Varying doses of BPA was orally administered daily from days 0 to 42. Anti-CII IgG2a antibodies and IFN-y secreted from splenic lymphocytes were measured as an indicator of Thl immune responses, while anti-CII IgGl antibodies and IL-4 as that of Th2 responses. The results showed that administration of BPA enhanced both the incidence and the severity of CIA. The enhancement of the disease was associated with pronounced production of anti-CII IgG and IgG2a antibodies. Treatment with DEP also augmented proliferative responses of spleen cells to CII. Both Thl and Th2 immune responses were significantly enhanced in mice exposed to BPA, although the enhancement of Thl responses appeared to be greater than that of Th2 responses. Augmentation of these immune responses was also observed in mice exposed to estradiol. These results suggest that exposure to BPA may influence autoimmune disease.