Immunological Complications of Radiation Combined Injury

放射联合损伤的免疫并发症

基本信息

批准号：
8117845
负责人：
JAMES A. LEDERER
金额：
$ 41.24万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-07-03 至 2013-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8117845
关键词：
Acetylcysteine Address Adjuvant Affect Agonist Allopurinol Animal Model Anti-Inflammatory Agents Anti-inflammatory Antibodies Antioxidants Area Bacterial Infections Blood Platelets Burn injury Cell physiology Cells Characteristics Clinical Data Communicable Diseases Competence Data Databases Development Dose Effectiveness Exposure to Failure Granulocyte Colony-Stimulating Factor Granulocyte-Macrophage Colony-Stimulating Factor HMGB1 gene Hematopoiesis Hematopoietic Cell Growth Factors Homeostasis Host Defense Human Immune Immune response Immune system Immunity Immunosuppressive Agents Individual Infection Inflammation Inflammatory Inflammatory Response Injury Intention Invaded Investigation Ligands Liquid substance Location Lung Measures Mediating Mediator of activation protein Modeling Molecular Mus Nuclear Accidents Opportunistic Infections Patients Peripheral Pharmaceutical Preparations Phase Phenotype Physiological Predisposition Radiation Radiation Injuries Recording of previous events Recovery Research Research Personnel Resuscitation Risk Rodent Sepsis Sepsis Syndrome Staging Stem Cell Factor Stress Syndrome T-Lymphocyte TLR2 gene TLR3 gene Testing Therapeutic Intervention Thrombopoietin Tissues Toll-like receptors Toxin Translational Research Trauma Treatment Effectiveness Uric Acid Vascular Endothelial Growth Factor Receptor-1 Work animal model development cancer therapy cytokine efficacy testing ethyl pyruvate experience immune function in vivo in vivo Model injured innovation insight microbial mortality mouse model outcome forecast pathogen pre-clinical prevent radiation effect research study response response to injury statistics therapy design wound xanthine oxidase inhibitor

项目摘要

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.

描述（由申请人提供）：核事故或袭击会造成辐射损伤和外伤，从而导致复合损伤。虽然复合损伤的程度根据受害者的位置而有所不同，但历史表明，与单一形式损伤的患者相比，经历复合损伤的个体更容易因损伤而死亡，并出现更严重的损伤后并发症。导致复合损伤受害者预后不良的机制尚不清楚。开发动物模型来研究复合损伤对免疫系统的影响将显着推进解决复合损伤免疫并发症的研究。因此，这一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，开发复合损伤小鼠模型。我们将收集由辐射、烧伤以及辐射与烧伤联合引起的小鼠免疫生理学变化的数据。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这种复合损伤小鼠模型来测试使用造血生长因子或Toll样受体佐剂诱导受伤小鼠免疫细胞恢复和增强宿主对病原体的防御的功效。在此阶段，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、烧伤或免疫系统联合损伤的有害影响。这些研究的结果将为我们和其他研究人员提供经过验证的辐射联合损伤小鼠模型，并将显着增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功效的实验结果将有助于了解哪种治疗干预可能对复合损伤受害者最有益。