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

慢性炎症似乎与癌症、心肌梗塞和其他疾病的发展显著相关。虽然原子弹投下已经过去了50多年，但原子弹幸存者患癌症、心脏病和糖尿病等“老年病”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，这可能会增加发生各种疾病的风险，我们使用原子弹幸存者的血液标本检测了IL-6，TNF-α，IFN-γ，CRP和IL-10的血浆水平，以审查其与辐射暴露剂量的关系。我们还开发了一个实用的测定系统，用于测量血清活性氧（ROS）水平的基础上使用多孔板，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著升高，并且ROS的产生随着辐射剂量的增加而显著且具有统计学意义地增加。ROS水平的增加与炎症标志物IL-6和CRP的增加成正比。此外，我们测量了暴露于辐射后小鼠淋巴细胞分数和炎症标志物水平的变化。该研究表明，在暴露的小鼠中，血液、胸腺、脾脏和淋巴结中的淋巴细胞数量减少，但在暴露和未暴露的小鼠之间，血浆中的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著差异。这些结果表明，感染引起的炎症，沿着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性炎症中发挥重要作用。

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.