gms | German Medical Science

Objectives: Bone fractures trigger an inflammatory cascade and immune system activation, playing a crucial role for effective healing outcome. However, inflammatory responses following trauma can also harm distant organs like the liver. With increasing age, the likelihood of bone fractures and a dysbalanced immune response following trauma rises, subsequently elevating the risks of organ injuries, infectious complications, and mortality. This study aims to examine early immune regulations in the liver of both young and old mice after femoral fracture.

Methods: Twenty-four male C57BL/6J mice were randomly and age-matched into four groups. Six young (17–26 weeks) and six aged (64–72 weeks) mice underwent femoral osteotomy with external fixation (Fx), while the remaining animals underwent sham procedures. Mice were sacrificed after 24 hours, and the effects on the liver were assessed through immunohistological examinations, gene expression, and protein analyses focusing on liver damage and inflammation.

Results and conclusion: Hematoxylin-eosin staining revealed that Fx did not induce liver damage, yet older mice generally displayed elevated damage levels. However, Fx increased the presence of caspase-3-positive cells and polymorphonuclear leukocytes (PMNL) infiltration, with aging exacerbating these effects. CXCL1 levels in the liver (gene expression, protein and histology) remained largely unaffected by Fx. Although Fx slightly raised TNF-a and IL-1b protein levels in liver tissue, the gene expression of IL6 and IL1b significantly increased only in old mice subjected to Fx. Overall, older mice exhibited higher basal levels of all examined proinflammatory cytokines. In contrast, Fx reduced the anti-inflammatory IL-10 in young animals, while aged mice from both treatments showed comparable IL-10 levels to young Fx animals. Fx diminished MCP-1, which was generally lower in aged mice. The DAMP receptor RAGE increased with Fx in both age groups, suggesting similarly susceptible to inflammatory stimuli production. Negative regulators of NFkB signaling and inflammation, SIRT1 and SIRT3, were elevated by Fx, but the magnitude observed in old mice was less pronounced than in young mice.

Our findings indicate that bone fractures induce liver damage and inflammation, though the observed effects were relatively modest. Regardless of trauma, susceptibility to liver damage and inflammation heightened with age. Although both young and old mice exhibited comparable sensitivity to inflammatory stimuli after trauma, the liver-protective signaling response and anti-inflammatory stimuli were diminished in old animals. The findings emphasize age-related distinctions in the liver's reaction to trauma-induced inflammation.