Aging effects on acute lung inflammation after burn injury

衰老对烧伤后急性肺部炎症的影响

• 批准号: 7276341
• 负责人: VANESSA NOMELLINI
• 金额: $ 2.69万
• 依托单位: LOYOLA UNIVERSITY CHICAGO
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7276341
• 关键词: Abbreviations; Acute; Adhesions; Adult Respiratory Distress Syndrome; Affect; Age; Alveolar; Antibodies; Antigens; Blood Circulation; Blood Vessels; Body Surface Area; Bronchoalveolar Lavage; Burn injury; CCL2 gene; CD31 Antigens; Cell Adhesion Molecules; Cells; Cessation of life; Data; Development; Distant; Elderly; Elevation; Endothelial Cells; Facial Injuries; Fluorescein; Fluorescein-5-isothiocyanate; Fluoresceins; Heart Diseases; Hematoxylin and Eosin Staining Method; Incidence; Individual; Infection; Inflammation; Inflammatory; Inflammatory Response; Injury; Intercellular adhesion molecule 1; Interleukin-10; Interleukin-6; Isothiocyanates; Leukocytes; Lung; Lung Inflammation; Lymphocyte Function-Associated Antigen-1; Malignant Neoplasms; Measures; Modeling; Monocyte Chemoattractant Protein-1; Morbidity - disease rate; Multiple Organ Failure; Mus; Neutrophil Infiltration; Numbers; Organ; Patients; Peroxidase; Persons; Phenotype; Play; Pneumonia; Population; Process; Production; Pulmonary Edema; Pulmonary Pathology; Recovery; Recruitment Activity; Relative (related person); Risk; Role; Secondary to; Site; Therapeutic; Tissues; Trauma; Treatment Protocols; Tumor Necrosis Factor-alpha; Tumor Necrosis Factors; Vascular Cell Adhesion Molecule-1; age effect; age group; aged; aging population; base; chemokine; cytokine; fluorouracil/semustine/vincristine protocol; human TNF protein; improved; integrin alpha1beta1; intraperitoneal; macrophage; macrophage inflammatory protein 2; mortality; neutrophil; older patient; prevent; response; size; therapeutic target; wound

DESCRIPTION (provided by applicant): The risk of complications and death after a moderate sized burn injury is significantly higher in persons over the age of 65, while almost non-existent in young, healthy individuals. The studies outlined below use a murine model of burn injury to help determine some of the mechanisms behind the development of pulmonary complications that frequently occur in aged individuals after burn injury. Our hypothesis is that, since aged mice maintain an elevated proinflammatory state prior to injury, they are at an even greater risk of pulmonary inflammation than young mice given a comparable sized wound and that this inflammatory response is a result of increased local production of neutrophil chemokines and expression of vascular adhesion molecules. In aim 1, we will assess various aspects of inflammation in lungs of young and aged mice after receiving a burn injury by examining 1) the number of neutrophils, 2) the degree of pulmonary edema, and 3) changes in the alveolar barrier function in lungs of mice from each age group. Aims 2 and 3 of the proposal will look at two possible mechanisms behind the observed neutrophil accumulation in the lungs of aged mice after burn: increased chemoattraction and higher expression of vascular adhesion molecules. Aim 2 will first involve, measuring levels of neutrophil chemokines in lungs from young and aged mice after burn injury to establish whether differences exist between the two age groups. To study the effects of these chemokines on neutrophil infiltration into the lungs, we will use antibodies to block those factors and examine the pulmonary consequences in young and aged mice after burn, as described in aim1. In aim 3, we will examine how endothelial adhesion affects pulmonary inflammation after burn. Initially we will analyze the relative expression levels of vascular adhesion molecules in the lungs obtained from young and aged mice after burn. To determine whether this process is important in modulating pulmonary inflammation, we will administer antibodies against vascular adhesion molecules and assess changes that occur in the inflammatory parameters in the lung as described above. The studies proposed in this application are critical to understanding why aged patients are at such a higher risk for pulmonary complications after burn injury. Although heart disease and cancer remain at the top of the list, injury and trauma continues to be a concern for our growing aging population. Uncovering the mechanisms behind the increased risk of complications in aged patients after injury may reveal targets for new and better therapeutic regimens that could potentially help older patients reach full recovery after suffering a burn injury.

描述（由申请人提供）：中度烧伤后并发症和死亡的风险在65岁以上的人中明显较高，而在年轻健康的人中几乎不存在。以下概述的研究使用烧伤的鼠模型来帮助确定烧伤后经常发生在老年人中的肺部并发症的发展背后的一些机制。我们的假设是，由于老年小鼠在损伤前保持升高的促炎状态，因此它们比具有可比大小的伤口的年轻小鼠具有更大的肺部炎症风险，并且这种炎症反应是嗜中性粒细胞趋化因子的局部产生增加和血管粘附分子表达增加的结果。在目的1中，我们将通过检查来自每个年龄组的小鼠的肺中的1）中性粒细胞的数量、2）肺水肿的程度和3）肺泡屏障功能的变化来评估在接受烧伤后的年轻和老年小鼠的肺中的炎症的各个方面。该提案的目标2和3将研究烧伤后老年小鼠肺中观察到的中性粒细胞积聚背后的两种可能机制：化学吸引力增加和血管粘附分子表达增加。目的2将首先涉及测量烧伤后年轻和老年小鼠肺中中性粒细胞趋化因子的水平，以确定两个年龄组之间是否存在差异。为了研究这些趋化因子对中性粒细胞浸润到肺部的影响，我们将使用抗体来阻断这些因子，并检查烧伤后年轻和老年小鼠的肺部后果，如aim 1所述。在目标3中，我们将研究内皮粘附如何影响烧伤后的肺部炎症。首先，我们将分析烧伤后从年轻和老年小鼠获得的肺中血管粘附分子的相对表达水平。为了确定这一过程在调节肺部炎症方面是否重要，我们将给予针对血管粘附分子的抗体，并评估如上所述肺部炎症参数发生的变化。本申请中提出的研究对于理解为什么老年患者在烧伤后肺部并发症的风险如此之高至关重要。虽然心脏病和癌症仍然排在首位，但伤害和创伤仍然是我们日益老龄化的人口所关注的问题。揭示老年患者受伤后并发症风险增加背后的机制可能会揭示新的和更好的治疗方案的目标，这些治疗方案可能有助于老年患者在遭受烧伤后完全康复。