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Age-dependent alterations in the inflammatory response to pulmonary challenge

Linge, Helena M LU ; Ochani, Kanta; Lin, Ke; Lee, Ji Young and Miller, Edmund J (2015) In Immunologic Research 63(1). p.15-209
Abstract

The aging lung is increasingly susceptible to infectious disease. Changes in pulmonary physiology and function are common in older populations, and in those older than 60 years, pneumonia is the major cause of infectious death. Understanding age-related changes in the innate and adaptive immune systems, and how they affect both pulmonary and systemic responses to pulmonary challenge are critical to the development of novel therapeutic strategies for the treatment of the elderly patient. In this observational study, we examined age-associated differences in inflammatory responses to pulmonary challenge with cell wall components from Gram-positive bacteria. Thus, male Sprague-Dawley rats, aged 6 months or greater than 18 months... (More)

The aging lung is increasingly susceptible to infectious disease. Changes in pulmonary physiology and function are common in older populations, and in those older than 60 years, pneumonia is the major cause of infectious death. Understanding age-related changes in the innate and adaptive immune systems, and how they affect both pulmonary and systemic responses to pulmonary challenge are critical to the development of novel therapeutic strategies for the treatment of the elderly patient. In this observational study, we examined age-associated differences in inflammatory responses to pulmonary challenge with cell wall components from Gram-positive bacteria. Thus, male Sprague-Dawley rats, aged 6 months or greater than 18 months (approximating humans of 20 and 55-65 years), were challenged, intratracheally, with lipoteichoic acid and peptidoglycan. Cellular and cytokine evaluations were performed on both bronchoalveolar lavage fluid (BAL) and plasma, 24 h post-challenge. The plasma concentration of free thyroxine, a marker of severity in non-thyroidal illness, was also evaluated. The older animals had an increased chemotactic gradient in favor of the airspaces, which was associated with a greater accumulation of neutrophils and protein. Furthermore, macrophage migration inhibitory factor (MIF), an inflammatory mediator and putative biomarker in acute lung injury, was increased in both the plasma and BAL of the older, but not young animals. Conversely, plasma free thyroxine, a natural inhibitor of MIF, was decreased in the older animals. These findings identify age-associated inflammatory/metabolic changes following pulmonary challenge that it may be possible to manipulate to improve outcome in the older, critically ill patient.

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publishing date
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Contribution to journal
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published
keywords
Adult, Age Factors, Aged, Animals, Chemotaxis, Humans, Lipopolysaccharides, Macrophage Migration-Inhibitory Factors, Male, Middle Aged, Neutrophils, Peptidoglycan, Pneumonia, Rats, Rats, Sprague-Dawley, Teichoic Acids, Thyroxine, Young Adult, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
in
Immunologic Research
volume
63
issue
1
pages
7 pages
publisher
Humana Press
external identifiers
  • scopus:84947491951
ISSN
0257-277X
DOI
10.1007/s12026-015-8684-7
language
English
LU publication?
no
id
e932c4e8-0dcb-4fb7-8576-219c644bfc4c
date added to LUP
2016-10-20 11:55:54
date last changed
2017-07-02 04:55:14
@article{e932c4e8-0dcb-4fb7-8576-219c644bfc4c,
  abstract     = {<p>The aging lung is increasingly susceptible to infectious disease. Changes in pulmonary physiology and function are common in older populations, and in those older than 60 years, pneumonia is the major cause of infectious death. Understanding age-related changes in the innate and adaptive immune systems, and how they affect both pulmonary and systemic responses to pulmonary challenge are critical to the development of novel therapeutic strategies for the treatment of the elderly patient. In this observational study, we examined age-associated differences in inflammatory responses to pulmonary challenge with cell wall components from Gram-positive bacteria. Thus, male Sprague-Dawley rats, aged 6 months or greater than 18 months (approximating humans of 20 and 55-65 years), were challenged, intratracheally, with lipoteichoic acid and peptidoglycan. Cellular and cytokine evaluations were performed on both bronchoalveolar lavage fluid (BAL) and plasma, 24 h post-challenge. The plasma concentration of free thyroxine, a marker of severity in non-thyroidal illness, was also evaluated. The older animals had an increased chemotactic gradient in favor of the airspaces, which was associated with a greater accumulation of neutrophils and protein. Furthermore, macrophage migration inhibitory factor (MIF), an inflammatory mediator and putative biomarker in acute lung injury, was increased in both the plasma and BAL of the older, but not young animals. Conversely, plasma free thyroxine, a natural inhibitor of MIF, was decreased in the older animals. These findings identify age-associated inflammatory/metabolic changes following pulmonary challenge that it may be possible to manipulate to improve outcome in the older, critically ill patient.</p>},
  author       = {Linge, Helena M and Ochani, Kanta and Lin, Ke and Lee, Ji Young and Miller, Edmund J},
  issn         = {0257-277X},
  keyword      = {Adult,Age Factors,Aged,Animals,Chemotaxis,Humans,Lipopolysaccharides,Macrophage Migration-Inhibitory Factors,Male,Middle Aged,Neutrophils,Peptidoglycan,Pneumonia,Rats,Rats, Sprague-Dawley,Teichoic Acids,Thyroxine,Young Adult,Journal Article,Research Support, N.I.H., Extramural,Research Support, Non-U.S. Gov't},
  language     = {eng},
  number       = {1},
  pages        = {15--209},
  publisher    = {Humana Press},
  series       = {Immunologic Research},
  title        = {Age-dependent alterations in the inflammatory response to pulmonary challenge},
  url          = {http://dx.doi.org/10.1007/s12026-015-8684-7},
  volume       = {63},
  year         = {2015},
}