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Age-associated changes in the inflammatory response to Gram-positive challenge of the lung
Critical Care volume 14, Article number: P8 (2010)
Mortality from sepsis is greater in the elderly than in the young although incidence only increases slightly. Pulmonary infections caused by Staphylococcus aureus that progress into sepsis are a major cause of death in elderly patients. Bacterial pneumonia is a common precipitating cause of sepsis. Gram-positive bacteria are increasing as causative agents of pneumonia in the elderly.
To investigate age-dependent changes in the intrapulmonary response to staphylococcal challenge.
Cell wall components lipoteichoic acid (LTA, 200 ng) and peptido-glycan (PGN, 660 ng) from S. aureus were instilled intratracheally to young (3 to 4 months) and old (> 18 months) C57Bl6 mice (n > 5/group). Controls received saline alone. After 6 hours, mice were euthanized by exsanguination, and blood saved for analysis. One-sided lavage was performed, the nonlavaged lung tissue collected and total RNA isolated.
Using this relatively mild challenge of LTA and PGN, we observed significant and age-dependent differences in the inflammatory response. Macrophage migration inhibitory factor (MIF) protein was significantly and age-dependently increased in BAL and plasma. A trend toward lower levels of total cells and neutrophils in the lung was noted in the old following stimulation, although the variation of the response was large. The dynamics of MIF at a transcriptional level in the lung was age-dependently altered, with a marked downregulation in the young mice after stimulation, whereas levels of MIF mRNA remained unchanged in the old mice. Transcriptional changes were also noted for the anti-inflammatory cytokine IL-10 and other mediators involved in lymphocyte, macrophage and neutrophil recruitment. Interestingly, explanted lung cells from young and old mice showed a similar expressional pattern, with atypical expression levels in cells originating from old mice lungs.
The findings support a hyperinflammatory response in the older individual at the measured time point. Interestingly, the differences were sustained in vitro in cells explanted from young and old mice. Together the data suggest an altered inflammatory response to infectious challenge of the aged lung. Explanted cells from old animals may be a valuable tool in determining age-dependent differences in inflammatory response and identifying novel targets for intervention.
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Linge, H., Ochani, K., Lin, K. et al. Age-associated changes in the inflammatory response to Gram-positive challenge of the lung. Crit Care 14, P8 (2010). https://doi.org/10.1186/cc9111
- Migration Inhibitory Factor
- Bacterial Pneumonia
- C57Bl6 Mouse
- Lipoteichoic Acid
- Measured Time Point