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.
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|Nomellini, Vanessa; Gomez, Christian R; Gamelli, Richard L et al. (2009) Aging and animal models of systemic insult: trauma, burn, and sepsis. Shock 31:11-20|
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