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

本研究旨在探讨包括双酚A(BPA)在内的内分泌干扰物对自身免疫性疾病的实验性模型--胶原性关节炎(CIA)的影响。用完全弗氏佐剂乳化的II型胶原(CII)皮下注射至尾部(第0天)，然后于第21天注射增强剂，诱导出CIA。从0天到42天，每天口服不同剂量的双酚A。检测脾淋巴细胞分泌的抗CIIIgG2a抗体和干扰素-γ作为Th1免疫应答的指标，抗CIIIgG1抗体和IL-4作为Th2免疫应答的指标。结果表明，双酚A的应用增加了CIA的发生率和严重程度。疾病的加强与显著的抗CII-Ig G和Ig G 2a抗体产生有关。DEP治疗也增强了脾细胞对CII的增殖反应。在暴露于双酚A的小鼠中，Th1和Th2免疫应答均显著增强，但Th1应答的增强似乎大于Th2应答。这些免疫反应在暴露于雌二醇的小鼠中也观察到了增强。这些结果表明，暴露于双酚A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.