Immunological Complications of Radiation Combined Injury

描述（由申请人提供）：核事故或袭击造成辐射伤害和创伤，导致复合伤害。然而，复合损伤的程度取决于受害者的位置，历史表明，经历复合损伤的个体比单一形式损伤的患者更容易屈服于他们的损伤，并产生更严重的伤后并发症。导致合并损伤患者预后不良的机制尚不清楚。研究联合损伤对免疫系统影响的动物模型的建立将显著推进联合损伤免疫并发症的研究。因此，这个分阶段创新项目的第一阶段将是通过探索不同剂量的辐射暴露和烧伤对免疫系统细胞和介质的影响，开发一个联合损伤的小鼠模型。我们将收集辐射、烧伤和辐射合并烧伤诱导小鼠免疫生理变化的数据。实验还将通过测试联合受伤小鼠抵抗细菌感染和败血症的能力来确定其免疫能力。该项目的第二阶段将使用该小鼠模型进行联合损伤，以测试使用造血生长因子或toll样受体佐剂诱导损伤小鼠免疫细胞恢复和增强宿主对病原体防御的功效。在这个阶段，我们还将测试使用抗炎治疗是否可以保护受伤的小鼠免受辐射、烧伤或免疫系统综合损伤的有害影响。这些研究的结果将为我们和其他研究者提供一个有效的辐射联合损伤小鼠模型，并将显著推进我们对联合损伤如何破坏免疫系统功能的理解。此外，测试免疫增强或抗炎治疗效果的实验结果将为了解哪种治疗干预可能对合并损伤患者最有益提供见解。

DESCRIPTION (provided by applicant): Nuclear accidents or attacks inflict both radiation injury and trauma resulting in a combined injury. While, the extent of the combined injury varies depending on the location of the victim, history indicates that individuals that experience combined injury succumb more readily to their injuries and develop more severe post-injury complications than patients with a single form of injury. The mechanisms responsible for the poor prognosis of combined injury victims are not know. The development of an animal model to study the effects of combined injury on the immune system would significantly advance research addressing the immune complications of combined injury. Therefore, the first phase of this phased innovation project will be to develop a mouse model for combined injury by exploring the effects of differing doses of radiation exposure and burn injury on cells and mediators of the immune system. We will collect data on immunophysiological changes in mice that are induced by radiation, by burn injury, and by combined radiation with burn injury. Experiments will also determine the immune competence of combined injured mice by testing their ability to resist bacterial infections and sepsis. The second phase this project will use this mouse model for combined injury to test the efficacy of using hematopoietic growth factor or Toll-like receptor adjuvants to induce immune cell recovery and stronger host defenses against pathogens in injured mice. During this phase, we will also test whether using counter-inflammatory treatments might protect injured mice from the detrimental effects of radiation, burn, or combined injury on the immune system. The results of these studies will provide us and other investigators with a validated mouse model for radiation combined injury and will significantly advance our understanding of how combined injury disrupts immune system function. Moreover, the findings of experiments testing the efficacy of immune-enhancing or counter-inflammatory treatments will provide insight into which therapeutic intervention might be the most beneficial to combined injury victims.