Immunological Complications of Radiation Combined Injury

放射复合损伤的免疫并发症

• 批准号: 7649465
• 负责人: JAMES A. LEDERER
• 金额: $ 16.87万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-03 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7649465
• 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

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. Nuclear accidents or attacks inflict radiation injury and trauma causing what is referred to as combined injury. Combined injury victims develop severe immune system failure, which makes them highly susceptible to dying of infections. This project will develop a mouse model for combined injury that will be used to advance our understanding of how combined injury affects the immune system and this new information will then be used to test the effectiveness of immune-enhancing drugs on their ability to restore normal immune system function in combined injury victims.

描述（由申请人提供）：核事故或攻击均造成辐射损伤和创伤，导致造成损伤。虽然综合伤害的程度取决于受害者的位置，但历史表明，经历损伤的人比单一形式受伤的患者更容易屈服于伤害，并产生更严重的伤害后并发症。不知道造成伤害受害者预后不良的机制。研究动物模型以研究联合损伤对免疫系统的影响的发展将显着提高研究，以解决联合损伤的免疫并发症。因此，该分阶段创新项目的第一阶段是通过探索不同剂量的辐射暴露和烧伤损伤对免疫系统的细胞和介体的影响来开发一种用于联合损伤的小鼠模型。我们将收集有关小鼠免疫生理变化的数据，这些数据是由辐射，烧伤以及辐射与烧伤损伤结合引起的。实验还将通过测试抗细菌感染和败血症的能力来确定损伤合并后的免疫能力。第二阶段该项目将使用该小鼠模型结合损伤，以测试使用造血生长因子或类似收费的受体佐剂诱导免疫细胞恢复和对损伤小鼠病原体的强宿主防御措施的功效。在此阶段，我们还将测试使用反炎症治疗是否可以保护受伤的小鼠免受免疫系统辐射，燃烧或综合损伤的不利影响。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小鼠模型，以进行辐射联合损伤，并会大大提高我们对损伤如何破坏免疫系统功能的理解。此外，测试免疫增强或反炎治疗功效的实验结果将提供有关哪种治疗干预措施可能对联合受伤受害者最有益的见解。核事故或攻击造成了辐射损伤和创伤，导致所谓的合并伤害。损伤的联合受害者造成严重的免疫系统衰竭，这使他们非常容易受到感染的死亡。该项目将开发出一种用于联合损伤的小鼠模型，该模型将用于提高我们对联合损伤如何影响免疫系统的理解，然后将使用该新信息来测试免疫增强药物的有效性，以恢复联合损伤受害者中正常免疫系统功能的能力。