Michael M Chen1, Jessica L Palmer2, Timothy P Plackett3, Cory R Deburghgraeve2, Elizabeth J Kovacs4. 1. Burn and Shock Trauma Research Institute, Loyola University Chicago Health Sciences Campus, 2160 S. 1st Avenue, Maywood, IL 60153, USA. 2. Burn and Shock Trauma Research Institute, Loyola University Chicago Health Sciences Campus, 2160 S. 1st Avenue, Maywood, IL 60153, USA; Department of Surgery, Loyola University Chicago Health Sciences Campus, 2160 S. 1st Avenue, Maywood, IL 60153, USA. 3. Department of Surgery, Loyola University Chicago Health Sciences Campus, 2160 S. 1st Avenue, Maywood, IL 60153, USA. 4. Burn and Shock Trauma Research Institute, Loyola University Chicago Health Sciences Campus, 2160 S. 1st Avenue, Maywood, IL 60153, USA; Department of Surgery, Loyola University Chicago Health Sciences Campus, 2160 S. 1st Avenue, Maywood, IL 60153, USA; Department of Microbiology and Immunology, Loyola University Chicago Health Sciences Campus, 2160 S. 1st Avenue, Maywood, IL 60153, USA; Immunology and Aging Program, Loyola University Chicago Health Sciences Campus, 2160 S. 1st Avenue, Maywood, IL 60153, USA. Electronic address: ekovacs@lumc.edu.
Abstract
BACKGROUND: Pseudomonas aeruginosa pneumonia is more common and more lethal in the elderly. The immunologic underpinnings of this increased incidence and mortality have not been evaluated, however are assumed to be a complication of age-associated immune dysfunction. METHODS: Young (10-12week old) and aged (18-20month old) BALB/c mice were subjected to intratracheal infection of P. aeruginosa. Animals were sacrificed 24h after inoculation. The lungs were collected for analysis of lung pathology, chemokine levels, neutrophil counts, and myeloperoxidase activity. RESULTS: Pulmonary levels of the neutrophil chemokine KC are significantly higher in aged mice relative to young following P. aeruginosa infection. Despite this, neutrophil counts are higher in young mice compared to aged mice after infection. Furthermore, the neutrophils are predominantly found in the air space of young infected mice. This correlated with increased myeloperoxidase activity from bronchoalveolar lavage specimens of young mice relative to aged mice after infection. CONCLUSIONS: Neutrophil migration into the lungs is impaired in aged mice 24h after intratracheal infection despite elevated chemokine levels, suggesting that immunosenescence is impairing neutrophil migration.
BACKGROUND:Pseudomonas aeruginosapneumonia is more common and more lethal in the elderly. The immunologic underpinnings of this increased incidence and mortality have not been evaluated, however are assumed to be a complication of age-associated immune dysfunction. METHODS: Young (10-12week old) and aged (18-20month old) BALB/c mice were subjected to intratracheal infection of P. aeruginosa. Animals were sacrificed 24h after inoculation. The lungs were collected for analysis of lung pathology, chemokine levels, neutrophil counts, and myeloperoxidase activity. RESULTS: Pulmonary levels of the neutrophil chemokine KC are significantly higher in aged mice relative to young following P. aeruginosa infection. Despite this, neutrophil counts are higher in young mice compared to aged mice after infection. Furthermore, the neutrophils are predominantly found in the air space of young infected mice. This correlated with increased myeloperoxidase activity from bronchoalveolar lavage specimens of young mice relative to aged mice after infection. CONCLUSIONS: Neutrophil migration into the lungs is impaired in aged mice 24h after intratracheal infection despite elevated chemokine levels, suggesting that immunosenescence is impairing neutrophil migration.
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