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Effects of Radiation Exposure on Reactive Oxygen Production in Vivo and Inflammatory Immune Response

辐射暴露对体内活性氧产生和炎症免疫反应的影响

基本信息

批准号：
15510065
负责人：
HAYASHI Tomonori
金额：
$ 2.37万
依托单位：
Radiation Effects Research Foundation
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15510065/
关键词：
ionizing radiation immunity inflammation cytokines reactive oxygen species CRP

项目摘要

Chronic inflammation seems to be significantly associated with development of cancer, myocardial infarction, and other diseases. Although more than fifty years have passed since the A-bomb was dropped, the risk for developing "diseases of aging" such as cancer, heart disease, and diabetes is still high among A-bomb survivors. On the assumption that effects of radiation exposure might have accelerated inflammation among A-bomb survivors, which may increase the risk of developing various diseases, we measured plasma levels of IL-6,TNF-α,IFN-γ,CRP, and IL-10 using blood specimens of A-bomb survivors to review their relationship with radiation exposure dose. We also developed a practical assay system for measurement of serum levels of reactive oxygen species(ROS) based on use of multi-well plates, and thereby investigated the effects of radiation exposure. As a result, we observed that the inflammation markers IL-6,TNF-α,IFN-γ,IL-10,and CRP were significantly elevated with increased radiation dose, and that the production of ROS significantly and statistically increased with increase of radiation dose. The increase in ROS levels was proportional to the increase of inflammatory markers IL-6 and CRP. In addition, we measured changes in lymphocyte fraction and inflammatory marker levels in mice after exposure to radiation. The study showed that the number of lymphocytes in the blood, thymus, spleen, and lymph nodes decreased in exposed mice, but there was no significant difference in inflammatory cytokines in the plasma or cellular cytokine levels in the thymus, spleen, or lymph nodes between exposed and non-exposed mice. These results suggest that inflammation induced by infection, along with decreased immunocompetent cells resulting from radiation exposure, may play an important role in the persistent inflammation observed among A-bomb survivors.

慢性炎症似乎与癌症、心肌梗塞和其他疾病的发生显着相关。尽管原子弹爆炸已经过去了五十多年，但原子弹幸存者罹患癌症、心脏病和糖尿病等“衰老疾病”的风险仍然很高。假设辐射暴露的影响可能会加速原子弹幸存者的炎症反应，从而增加患各种疾病的风险，我们使用原子弹幸存者的血液样本测量了IL-6、TNF-α、IFN-γ、CRP和IL-10的血浆水平，以回顾其与辐射暴露剂量的关系。我们还开发了一种实用的检测系统，用于基于多孔板测量血清活性氧（ROS）水平，从而研究辐射暴露的影响。结果，我们观察到炎症标志物IL-6、TNF-α、IFN-γ、IL-10和CRP随着辐射剂量的增加而显着升高，并且ROS的产生随着辐射剂量的增加而显着且统计学上增加。 ROS水平的增加与炎症标志物IL-6和CRP的增加成正比。此外，我们还测量了小鼠暴露于辐射后淋巴细胞分数和炎症标志物水平的变化。研究表明，暴露小鼠的血液、胸腺、脾脏和淋巴结中的淋巴细胞数量减少，但暴露小鼠和未暴露小鼠的血浆中炎性细胞因子或胸腺、脾脏或淋巴结中的细胞因子水平没有显着差异。这些结果表明，感染引起的炎症，以及辐射暴露导致的免疫活性细胞减少，可能在原子弹幸存者中观察到的持续炎症中发挥重要作用。