Immunological Complications of Radiation Combined Injury

放射联合损伤的免疫并发症

• 批准号: 8321044
• 负责人: JAMES A. LEDERER
• 金额: $ 39.02万
• 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 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8321044
• 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; TLR7 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.

描述（由申请人提供）：核事故或核攻击造成辐射损伤和创伤，导致复合损伤。虽然，复合伤的程度取决于受害者的位置，历史表明，经历复合伤的人更容易屈服于他们的伤害，并发展更严重的伤后并发症比单一形式的伤害的患者。复合伤患者预后不良的机制尚不清楚。研究复合伤对免疫系统影响的动物模型的开发将显著推进复合伤免疫并发症的研究。因此，该阶段性创新项目的第一阶段将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，开发一种复合损伤的小鼠模型。我们将收集有关辐射、烧伤和辐射与烧伤联合诱导的小鼠免疫生理学变化的数据。实验还将通过测试复合损伤小鼠抵抗细菌感染和脓毒症的能力来确定其免疫能力。该项目的第二阶段将使用该复合损伤小鼠模型来测试使用造血生长因子或Toll样受体佐剂诱导损伤小鼠的免疫细胞恢复和更强的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，烧伤或联合损伤对免疫系统的不利影响。这些研究的结果将为我们和其他研究人员提供一个经过验证的放射性复合损伤小鼠模型，并将显着推进我们对复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提供对哪种治疗干预可能对复合损伤受害者最有益的见解。