Effect of total body irradiation on late lung effects: Hidden dangers
Effect of total body irradiation on late lung effects: Hidden dangers
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DOI：
10.3109/09553002.2011.573439
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发表时间：
2011-08-01
影响因子：
2.6
通讯作者：
Williams, Jacqueline P.
中科院分区：
文献类型：
--
作者：
Johnston, Carl J.;Manning, Casey;Williams, Jacqueline P.
目的：在我们对放射性恐怖主义或核扩散事件后果的持续调查中，我们评估了被认为是肺部终点发展的亚阈值的剂量范围是否会导致晚期病理变化，其次，这些晚期变化是否会影响肺部应对后续挑战的能力。材料和方法：C57BL/6J 小鼠接受全身照射（0.5-10 Gy），并在照射后随访 6-18 个月。在 12 个月和 15 个月时，一部分小鼠接受了第二次攻击（气雾化脂多糖 [LPS]）。结果：细胞因子显示在照射后早期（几小时）上调（白细胞介素 [IL] 6、角质形成细胞趋化剂 [KC]、IL1B 和 IL1R2），证明信使核糖核酸 (mRNA) 表达在后期（从 9 个月开始）的时间点有所增加。尽管观察到 T 细胞计数持续、剂量依赖性增加，但没有观察到病理生理学的其他明显变化。尽管如此，在较晚的时间点暴露于二次攻击的动物表现出相对于对照组，炎症细胞募集和反应持续性增加。结论：我们提出，在引起病理生理学变化很小的剂量后，亚临床辐射引起的损伤可能通过辐射引起的免疫防御系统的改变而增加肺部对二次攻击的易感性。
Purpose: In our ongoing investigation into the consequences of a radiological terrorism or nuclear dispersion event, we assessed whether a dose range that is believed to be sub-threshold for the development of lung endpoints results in late pathological changes and, secondarily, whether those late changes affect the lung's ability to respond to subsequent challenge.Materials and methods: C57BL/6J mice received total body irradiation (0.5-10 Gy) and were followed for 6-18 months after irradiation. At 12 and 15 months, a subset of mice was exposed to a second challenge (aerosolised lipopolysaccharide [LPS]).Results: Cytokines shown to be upregulated early (hours) following irradiation (interleukin [IL] 6, keratinocyte chemoattractant [KC], IL1B, and IL1R2) demonstrated increases in messenger ribose nucleic acid (mRNA) expression at late time points, beginning at nine months. Although persistent, dose-dependent increases in T cell counts were seen, no other overt changes in pathophysiology were observed. Nonetheless, animals that were exposed to a secondary challenge at late time points demonstrated an increased inflammatory cell recruitment and persistence in response relative to controls.Conclusions: We propose that, following doses that elicit little change in pathophysiology, sub-clinical radiation-induced injury increases the lungs' susceptibility to a secondary challenge, possibly through a radiation-induced alteration in the immune defense system.