Acute radiation syndrome (ARS) - treatment of the reduced host defense.
Acute radiation syndrome (ARS) - treatment of the reduced host defense.
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DOI：
10.2147/ijgm.s22177
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发表时间：
2012
影响因子：
2.3
通讯作者：
Nepper-Christensen S
中科院分区：
文献类型：
--
作者：
Heslet L;Bay C;Nepper-Christensen S
福岛核电站事故的辐射威胁促使人们重新思考预防和治疗急性辐射综合征（ARS）的应急计划。在美国，生长因子（粒细胞集落刺激因子[G-CSF]和粒细胞-巨噬细胞集落刺激因子[GM-CSF]）在急性辐射损伤中的作用已得到充分证实，这是基于生长因子增加巨噬细胞和粒细胞的数量和功能的事实。当前文献综述。肺有自己的宿主防御系统，以肺泡巨噬细胞为基础。在辐射暴露于肺后，静止的巨噬细胞不能再转化，甚至在全身施用生长因子期间也不能，因为G-CSF/GM-CSF不能穿透肺泡。在正常情况下，局部产生的GM-CSF受体将静息巨噬细胞转化为封闭的肺室中的完全免疫活性的树突状细胞。然而，由于巨噬细胞的退热，GM-CSF在辐射损伤的组织中不表达。为了维持巨噬细胞在辐射暴露后在宿主防御中的重要作用，假设有必要外源性地施用药物以维持对外源性和内源性感染的屏障，并可能预防可能致命的全身感染，这是ARS中死亡的主要原因。在疑似暴露于至少<2戈伊的辐射剂量后，应立即全身给予250-400 μg GM-CSF/m2或5 μg/kg G-CSF，同时每天吸入< 300 mcg GM-CSF，持续至少14-21天，开始预先治疗。因此，美国目前预防和治疗ARS的标准干预措施应修改为联合全身施用生长因子和吸入GM-CSF，以确保持续的全身和肺部宿主防御，从而预防肺功能障碍。
The current radiation threat from the Fukushima power plant accident has prompted rethinking of the contingency plan for prophylaxis and treatment of the acute radiation syndrome (ARS). The well-documented effect of the growth factors (granulocyte colony-stimulating factor [G-CSF] and granulocyte-macrophage colony-stimulating factor [GM-CSF]) in acute radiation injury has become standard treatment for ARS in the United States, based on the fact that growth factors increase number and functions of both macrophages and granulocytes. Review of the current literature. The lungs have their own host defense system, based on alveolar macrophages. After radiation exposure to the lungs, resting macrophages can no longer be transformed, not even during systemic administration of growth factors because G-CSF/GM-CSF does not penetrate the alveoli. Under normal circumstances, locally-produced GM-CSF receptors transform resting macrophages into fully immunocompetent dendritic cells in the sealed-off pulmonary compartment. However, GM-CSF is not expressed in radiation injured tissue due to defervescence of the macrophages. In order to maintain the macrophage’s important role in host defense after radiation exposure, it is hypothesized that it is necessary to administer the drug exogenously in order to uphold the barrier against exogenous and endogenous infections and possibly prevent the potentially lethal systemic infection, which is the main cause of death in ARS. Preemptive treatment should be initiated after suspected exposure of a radiation dose of at least <2 Gy by prompt dosing of 250–400 μg GM-CSF/m2 or 5 μg/kg G-CSF administered systemically and concomitant inhalation of GM-CSF < 300 mcg per day for at least 14–21 days. The present United States standard for prevention and treatment of ARS standard intervention should consequently be modified into the combined systemic administration of growth factors and inhaled GM-CSF to ensure the sustained systemic and pulmonary host defense and thus prevent pulmonary dysfunction.