Department of Microbiology, School of Pharmaceutical Sciences, Kyushu University of Health and Welfare, Yoshino 1714-1, Nobeoka, Miyazaki 882-8508, Japan.
Int Immunopharmacol. 2010 Apr;10(4):393-7. doi: 10.1016/j.intimp.2009.12.014. Epub 2010 Jan 13.
Effects of the brominated flame retardants (BFRs), decabrominated diphenyl ether (DBDE), hexabromocyclododecane (HBCD), and tetrabromobisphenol A (TBBPA), on host immunity of mice were evaluated using respiratory syncytial virus (RSV) infection. Five-week-old female mice were fed a diet containing 1% BFRs for 28days, and subsequently infected with RSV. No toxicological sign was observed in BFR-treated mice before infection. TBBPA significantly increased the pulmonary viral titer in the infected mice on day 5 post-infection, but DBDE and HBCD did not. Slight histological changes were observed in lung tissues of TBBPA-treated mice with mock infection. These changes due to TBBPA were much exacerbated by RSV infection. Cytokine analysis of bronchoalveolar lavage fluid (BALF) from RSV-infected mice treated with or without TBBPA revealed that TBBPA significantly increased the levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6 and interferon (IFN)-gamma at each time point after virus infection, but no change was observed for IL-1beta and IL-12. The levels of IL-4 and IL-10, Th2 cytokines, significantly decreased. Thus, TBBPA caused unusual production of the various cytokines in RSV-infected mice. Flow cytometry revealed that the percentage of double-positive CD4+CD8+ cells, immature T lymphocytes, in the cell populations in BALF from RSV-infected mice increased due to TBBPA treatment. The change was not observed in spleen cells of TBBPA-treated mice. The response to RSV infection verified that TBBPA treatment affected the host immunity of mice. Irregular changes in cytokine production and immune cell populations due to TBBPA treatment were suggested to cause exacerbation of pneumonia in RSV-infected mice.
采用呼吸道合胞病毒（RSV）感染的方法，评价溴系阻燃剂（BFRs），十溴二苯醚（DBDE）、六溴环十二烷（HBCD）和四溴双酚 A（TBBPA）对宿主免疫的影响。将 5 周龄雌性小鼠用含 1% BFRs 的饲料喂养 28 天，然后感染 RSV。在感染前，BFR 处理的小鼠没有观察到毒性迹象。TBBPA 显著增加了感染后第 5 天感染小鼠的肺部病毒滴度，但 DBDE 和 HBCD 没有。在假感染的 TBBPA 处理的小鼠的肺组织中观察到轻微的组织学变化。这些变化因 RSV 感染而加剧。用或不用 TBBPA 处理感染 RSV 的小鼠的支气管肺泡灌洗液（BALF）的细胞因子分析表明，TBBPA 在病毒感染后每个时间点均显著增加肿瘤坏死因子（TNF）-α、白细胞介素（IL）-6 和干扰素（IFN）-γ的水平，但 IL-1β 和 IL-12 没有变化。Th2 细胞因子 IL-4 和 IL-10 的水平显著降低。因此，TBBPA 导致感染 RSV 的小鼠产生各种异常细胞因子。流式细胞术显示，由于 TBBPA 处理，感染 RSV 的小鼠 BALF 细胞群中 CD4+CD8+双阳性细胞、未成熟 T 淋巴细胞的百分比增加。TBBPA 处理的小鼠脾细胞中未观察到这种变化。对 RSV 感染的反应证实，TBBPA 处理影响了小鼠的宿主免疫。由于 TBBPA 处理导致细胞因子产生和免疫细胞群的不规则变化，可能导致感染 RSV 的小鼠肺炎恶化。
