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Age influences inflammatory responses, hemodynamics, and cardiac proteasome activation during acute lung injury

Linge, Helena M LU ; Lee, Ji Young; Ochani, Kanta; Koga, Kiyokazu; Kohn, Nina; Ojamaa, Kaie; Powell, Saul R and Miller, Edmund J (2015) In Lung 41(4). p.27-216
Abstract

BACKGROUND: Acute lung injury (ALI) is a significant source of morbidity and mortality in critically ill patients. Age is a major determinant of clinical outcome in ALI. The increased ALI-associated mortality in the older population suggests that there are age-dependent alterations in the responses to pulmonary challenge. The objective of this observational study was to evaluate age-dependent differences in the acute (within 6 hours) immunological and physiological responses of the heart and lung, to pulmonary challenge, that could result in increased severity.

METHODS: Male C57Bl/6 mice (young: 2-3 months, old: 18-20 months) were challenged intratracheally with cell wall components from Gram-positive bacteria (lipoteichoic acid... (More)

BACKGROUND: Acute lung injury (ALI) is a significant source of morbidity and mortality in critically ill patients. Age is a major determinant of clinical outcome in ALI. The increased ALI-associated mortality in the older population suggests that there are age-dependent alterations in the responses to pulmonary challenge. The objective of this observational study was to evaluate age-dependent differences in the acute (within 6 hours) immunological and physiological responses of the heart and lung, to pulmonary challenge, that could result in increased severity.

METHODS: Male C57Bl/6 mice (young: 2-3 months, old: 18-20 months) were challenged intratracheally with cell wall components from Gram-positive bacteria (lipoteichoic acid and peptidoglycan). After 6 hours, both biochemical and physiological consequences of the challenge were assessed. Alveolar infiltration of inflammatory cells and protein, airspace and blood cytokines, cardiac function and myocardial proteasome activity were determined.

RESULTS: In young mice, there was a dose-dependent response to pulmonary challenge resulting in increased airspace neutrophil counts, lung permeability, and concentrations of cytokines in bronchoalveolar lavage fluid and plasma. A midrange dose was then selected to compare the responses in young and old animals. In comparison, the old animals displayed increased neutrophil accumulation in the airspaces, decreased arterial oxygen saturation, body temperatures, plasma cytokine concentrations, and a lack of myocardial proteasome response, following challenge.

CONCLUSIONS: Age-dependent differences in the onset of systemic response and in maintenance of vital functions, including temperature control, oxygen saturation, and myocardial proteasome activation, are evident. We believe a better understanding of these age-related consequences of ALI can lead to more appropriate treatments in the elderly patient population.

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published
keywords
Acute Lung Injury, Age Factors, Aging, Animals, Bronchoalveolar Lavage Fluid, Cytokines, Disease Models, Animal, Hemodynamics, Inflammation Mediators, Lipopolysaccharides, Lung, Male, Mice, Inbred C57BL, Myocardium, Neutrophil Infiltration, Peptidoglycan, Pneumonia, Proteasome Endopeptidase Complex, Risk Factors, Severity of Illness Index, Teichoic Acids, Time Factors, Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
in
Lung
volume
41
issue
4
pages
12 pages
publisher
Springer
external identifiers
  • scopus:84928481598
ISSN
1432-1750
DOI
10.3109/01902148.2014.999174
language
English
LU publication?
no
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7eb3352a-1280-47e2-bcc0-a25f4068a076
date added to LUP
2016-10-20 11:54:43
date last changed
2017-10-22 05:20:46
@article{7eb3352a-1280-47e2-bcc0-a25f4068a076,
  abstract     = {<p>BACKGROUND: Acute lung injury (ALI) is a significant source of morbidity and mortality in critically ill patients. Age is a major determinant of clinical outcome in ALI. The increased ALI-associated mortality in the older population suggests that there are age-dependent alterations in the responses to pulmonary challenge. The objective of this observational study was to evaluate age-dependent differences in the acute (within 6 hours) immunological and physiological responses of the heart and lung, to pulmonary challenge, that could result in increased severity.</p><p>METHODS: Male C57Bl/6 mice (young: 2-3 months, old: 18-20 months) were challenged intratracheally with cell wall components from Gram-positive bacteria (lipoteichoic acid and peptidoglycan). After 6 hours, both biochemical and physiological consequences of the challenge were assessed. Alveolar infiltration of inflammatory cells and protein, airspace and blood cytokines, cardiac function and myocardial proteasome activity were determined.</p><p>RESULTS: In young mice, there was a dose-dependent response to pulmonary challenge resulting in increased airspace neutrophil counts, lung permeability, and concentrations of cytokines in bronchoalveolar lavage fluid and plasma. A midrange dose was then selected to compare the responses in young and old animals. In comparison, the old animals displayed increased neutrophil accumulation in the airspaces, decreased arterial oxygen saturation, body temperatures, plasma cytokine concentrations, and a lack of myocardial proteasome response, following challenge.</p><p>CONCLUSIONS: Age-dependent differences in the onset of systemic response and in maintenance of vital functions, including temperature control, oxygen saturation, and myocardial proteasome activation, are evident. We believe a better understanding of these age-related consequences of ALI can lead to more appropriate treatments in the elderly patient population.</p>},
  author       = {Linge, Helena M and Lee, Ji Young and Ochani, Kanta and Koga, Kiyokazu and Kohn, Nina and Ojamaa, Kaie and Powell, Saul R and Miller, Edmund J},
  issn         = {1432-1750},
  keyword      = {Acute Lung Injury,Age Factors,Aging,Animals,Bronchoalveolar Lavage Fluid,Cytokines,Disease Models, Animal,Hemodynamics,Inflammation Mediators,Lipopolysaccharides,Lung,Male,Mice, Inbred C57BL,Myocardium,Neutrophil Infiltration,Peptidoglycan,Pneumonia,Proteasome Endopeptidase Complex,Risk Factors,Severity of Illness Index,Teichoic Acids,Time Factors,Comparative Study,Journal Article,Research Support, N.I.H., Extramural,Research Support, Non-U.S. Gov't},
  language     = {eng},
  number       = {4},
  pages        = {27--216},
  publisher    = {Springer},
  series       = {Lung},
  title        = {Age influences inflammatory responses, hemodynamics, and cardiac proteasome activation during acute lung injury},
  url          = {http://dx.doi.org/10.3109/01902148.2014.999174},
  volume       = {41},
  year         = {2015},
}