Department of Biochemistry, School of Pharmaceutical Sciences, Kyushu University of Health and Welfare, Yoshino 1714-1, Nobeoka, Miyazaki 882-8508, Japan.
Environ Toxicol Pharmacol. 2008 Jan;25(1):69-74. doi: 10.1016/j.etap.2007.09.003. Epub 2007 Sep 15.
We evaluated the effect of 6-propyl-2-thiouracil (PTU), an anti-thyroid agent, on developmental immunity using respiratory syncytial virus (RSV) infection to offspring mice as a new risk assessment for brominated flame retardants (BFRs), because some BFRs are suspected of affecting the thyroid system. Pregnant mice were exposed to PTU in drinking water from gestation day 10 to weaning on postnatal day 21. Their offspring mice were infected intranasally with RSV. Exposure of 100ppm PTU significantly increased virus titers in the lungs of RSV-infected offspring compared with the control, and the 10ppm also elevated levels of interferon-γ, a marker of pneumonia, in the bronchoalveolar lavage fluids of offspring. Histopathological analysis revealed that PTU-exposure exacerbated pneumonia in RSV-infected offspring. Thus, exacerbation of RSV infection suggested PTU-exposure of dams elicited developmental immune disorder in the offspring. The murine RSV infection model may be useful to evaluate the developmental immunotoxicity of BFRs.
我们评估了抗甲状腺药物 6-丙基-2-硫代尿嘧啶（PTU）对发育免疫的影响，使用呼吸道合胞病毒（RSV）感染后代小鼠作为溴系阻燃剂（BFRs）的新风险评估，因为一些 BFRs 被怀疑会影响甲状腺系统。从妊娠第 10 天到产后第 21 天断奶，给怀孕的老鼠在饮用水中摄入 PTU。它们的后代小鼠通过鼻腔内感染 RSV。与对照组相比，暴露于 100ppm PTU 会显著增加 RSV 感染后代肺部的病毒滴度，而 10ppm 也会提高支气管肺泡灌洗液中肺炎的标志物干扰素-γ的水平。组织病理学分析显示，PTU 暴露使 RSV 感染的后代肺炎加重。因此，RSV 感染的加剧表明母体暴露于 PTU 会使后代的发育免疫紊乱。鼠类 RSV 感染模型可能有助于评估 BFRs 的发育免疫毒性。
