Artikel
Age-dependent elevated pulmonary CXCL-1 levels lead to an increased remote lung damage after femoral fracture in a murine model
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Veröffentlicht: | 21. Oktober 2024 |
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Gliederung
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Objectives: The relevance of age-related functional changes in patients experiencing fractures has increased due to the global rise in life expectancy and the elevated risk of fractures in the aging population. Various physiological alterations related to age have been identified, including those affecting bone-healing and immunological functions. The potential crosstalk between long-bone fractures and the respiratory system is particularly crucial in a clinical context, given the high incidence of pneumonia in aged patients with fractures and its impact on mortality. This murine experimental study was conducted to explore how age influences the distant interaction between long-bone fractures and the lungs.
Methods: Male C57BL/6J mice aged 17–26 weeks (young mice, n=6) and 64–72 weeks (aged mice, n=6) underwent isolated femur fracture followed by external fixation. Sham animals underwent the operative procedures without fracture induction. The animals were euthanized 24 hours after fracture induction, and pulmonary protein expressions of CXCL-1, IL-6, and MCP-1 were measured. Lung damage was assessed by analyzing total protein levels in bronchoalveolar lavage fluid (BAL), histological pulmonary neutrophil infiltration, and RAGE expression.
Results: Baseline expressions of CXCL-1 and IL-6 were higher in aged mice, while MCP-1 was lower. Fracture induction resulted in reduced expression of CXCL-1 and IL-6 in both young and aged animals, with levels in aged animals remaining higher than those in young animals. While pulmonary neutrophil infiltration slightly decreased in young animals with fractures compared to sham, an increase was observed in aged animals following fracture induction. This was associated with increased pulmonary damage, as evidenced by heightened RAGE expression and elevated total protein levels in BAL.
Conclusion: Baseline levels of key pulmonary inflammatory parameters vary in the elderly. Elevated baseline levels of CXCL-1, acting as a migratory stimulus for neutrophils, were linked to increased pulmonary neutrophil infiltration following fracture induction. Consequently, baseline alterations in the elderly can influence the remote cell migration pattern after a fracture, exacerbating pulmonary damage. These changes may contribute to the development of pulmonary complications in elderly individuals with fractures.