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Neutrophil recruitment by macrophage migration inhibition factor and CXCL1 to the lung following staphylococcal stimulation is significantly elevated in advanced age
Critical Care volume 13, Article number: P54 (2009)
Mortality from sepsis is greater in the elderly than in the young although incidence only increases slightly. Pulmonary infections caused by Staphylococcus aureus, which progress into sepsis, are a major cause of death in elderly patients. Adiponectin, multifaceted adipokine with anti-inflammatory properties, is secreted primarily from adipose tissue. It is increasingly acknowledged that the tissue microenvironment changes with old age. With increasing age, ectopic fat accumulates, increasing the possibility of elevated levels of adipose-derived mediators in the older individual.
To investigate age-dependent changes in the intra-pulmonary response to staphylococcal challenge. We hypothesized that older animals have higher levels of adiponectin due to adipose tissue accumulation and that these levels will neutralize the proinflammatory consequences of staphylococcal stimulation of the lung.
Young (6 months) and old (>18 months) male Sprague-Dawley rats were challenged intratracheally with S. aureus cell wall components lipoteichoic acid (LTA, 0.15 mg) and peptidoglycan (PGN, 0.5 mg) or saline alone. After 24 hours, plasma was collected and lungs lavaged post mortem. Concentrations of total protein, chemokines and MIF were assessed. In vitro studies examined the accumulation of adiponectin in the culture medium of the adipocyte cell line 3T3-L1 following direct challenge with LTA/PGN (3 μg/ml; 100 μg/ml) for 6 hours.
The older age group, compared with the young group receiving the same stimulus, showed significantly elevated alveolar levels of MIF and CXCL1 (KC), both involved in neutrophil recruitment. Neutrophils (controls: 0.029 ± 0.033, young: 13.9 ± 7.8, old: 29.3 ± 10.5, × 106) and the total number of cells (controls: 0.72 ± 0.26, young: 16.4 ± 9.7, old: 32.9 ± 11.2, × 106) within the alveolar space were significantly and age-dependently increased, following pulmonary insult. Plasma adiponectin did not change significantly. However, instillation of LTA/PGN significantly elevated the levels of adiponectin found within the alveolar space (controls: 3.9 ± 2.4, young: 22.5 ± 8.8, old: 29 ± 10.8 ng/ml, P < 0.01). Interestingly, following LTA/PGN challenge of adipocytes, there was a significant decrease in adiponectin concentration in the culture medium (control: 20.3 ± 0.78, LTA/PGN: 18.23 ± 1.14 pg/ml, P = 0.016).
The proinflammatory but not anti-inflammatory components of the immune response (assessed by neutrophil recruitment and adiponectin concentrations, respectively) differed significantly between the age groups. Since adiponectin decreased on direct stimulation of adipocytes, the increased adiponectin within the lungs may reflect increased lung permeability, and/or production by other cells within the lung. These findings are important in understanding the response to pulmonary infections in the older patient and may lead to the identification of novel targets for age-dependent therapeutic strategies.
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Linge, H., Takahashi, K. & Miller, E. Neutrophil recruitment by macrophage migration inhibition factor and CXCL1 to the lung following staphylococcal stimulation is significantly elevated in advanced age. Crit Care 13, P54 (2009). https://doi.org/10.1186/cc8124
- Migration Inhibition Factor
- Pulmonary Infection
- Neutrophil Recruitment
- Alveolar Space
- Plasma Adiponectin