gms | German Medical Science

Objectives: Trauma is a significant cause of mortality and disability worldwide. Traumatic injury induces systemic and local inflammation that can affect distant organs, notably lungs. Aging compromises the immune system and my lead to impaired regulatory mechanisms of posttraumatic inflammation, potentially promoting the susceptibility of aged traumatized patients for detrimental outcomes. We hypothesize that aging exacerbates the posttraumatic systemic inflammatory response and apoptosis, which in turn exacerbates the disruption of lung barrier integrity after trauma.

Methods: Animals in the control sham groups (sham young: n=6; sham aged n=6) were subjected to femoral artery catheterization and underwent an external fixator, but no osteotomy or blood loss were induced. Hemorrhagic shock (HS) was induced in trauma groups and external fixator followed by osteotomy were applied (THFx young: n=6; THFx old n=6). Histological lung injury score (LIS) was assessed to analyze the trauma-induced lungy damge. Gene expression of Cxcl1, Il-1β, Muc5ac, Tnf and Tnfrsf10b, as well as CXCL1, IL-1β protein levels in the lung tissue and bronchoalveolar lavage fluid were determined by RT-qPCR, ELISA, and immunohistology. Infiltrating polymorphonuclear leukocytes (PMNL) were examined via immunohistological staining. Apoptosis was detected by activated caspase-3 expression in the lung tissue.

Results and conclusion: Gene expression of the lung protective protein Muc5ac in THFx groups was significantly lower than in sham groups. THFx aged group showed a significantly lower gene expression of Muc5ac than the THFx young group. Caspase-3 positive cells in THFx groups were significantly higher compoared to the corresponding sham groups, and notably the number of caspase-3 positive cells in THFx aged group was significantly increased versus THFx young group. CXCL1 protein expression, as well as its concentration in the BALF and gene expression of CXCL1 in the lungs was significantly increased in the THFx young group compared with other groups. Aging increased the expression of inflammation-related markers such as IL-1β and NLRP3 after trauma, as well as the infiltration of PMNL in lungs.

After femur fracture and hemorrhagic shock in mice, aging exacerbates the disruption of the pulmonary barrier, and thus may cause a more severe systemic and local inflammatory response, exacerbating posttraumatic distal lung apoptosis and lung injury.