The immune response after fracture trauma is different in old compared to young patients

Abstract

Background: Despite significant medical progress and improved treatment, surgical procedures of proximal femur fractures in older patients are still associated with a high postoperative complication and mortality rate. Recently, several authors investigated the phenomenon of immunoageing, indicating differences in the ageing immune system. The aim of the present multi-center prospective clinical trial was to analyze differences in the posttraumatic immune response of old patients compared to young patients.

Methods: Blood was collected from young patients (<50 y, n = 20) with long bone fractures (YF), old patients (>70 y, n = 21) with proximal femur fractures (OF) upon clinical admission and within 6 hours after surgery, and two healthy age matched control groups (YH & OH). Serum TRAIL- and cytokine concentrations were analyzed via cytometric bead array, Fas-Ligand and TNF-Receptor-I via ELISA. CD15(+) magnetic bead-isolated neutrophils (PMN) were TUNEL stained.

Results: IL-6 was significantly increased only in OF after trauma and surgery whereas YF patient exhibited a marked decrease of TNF after trauma. Interestingly, a significant increase of GM-CSF serum levels was observed in YF only, whereas OF exhibited a decrease of systemic IFN-γ concentrations after trauma and after surgery. The healthy controls, old and young, had more or less similar inflammation levels. Moreover, TRAIL serum levels were diminished in OF after trauma and even further after surgery whereas in YF this was only observed after the surgical procedure. Fas-L concentrations were reduced only in YF after surgery or trauma. PMN apoptosis was significantly reduced only in YF, indicating activation of the innate immune system.

Discussion: In summary, our data suggest that the posttraumatic immune response is differently regulated in old and young trauma patients. The operative procedure further impacts these differences after trauma. Whether the decreased activation of PMNs and phagocytes along with the observed dysregulation of the posttraumatic inflammatory response contributes to the high perioperative mortality rate of the elderly suffering from a proximal femoral fracture requires further investigation.

Keywords: Apoptosis; Immunoageing; Inflammation; Trauma.

Figure 1

IL-6 and IL-8 levels. A While the young and old controls showed nearly similar IL-6 levels, trauma and surgery led to a significant increase in old patients compared to controls while serum levels in the young patients did not change markedly (p < 0.05, ANOVA on Ranks). B No significant differences in IL-8 levels could be detected.

Figure 2

TNF-α, IFN-γ and GM-CSF levels. A While TNF-α was significantly decreased in young patients after trauma and surgery, the old patients showed a reduction only after surgery compared to the healthy control respectively (p < 0.05, ANOVA on ranks). B In contrast IFN-γ concentrations were significantly reduced in old patients after trauma and surgery while no changes could be detected in young patients compared to healthy controls respectively (p < 0.05, Anova on ranks). C Young patients experienced an immediate increase of GM-CSF levels after trauma. This was not observed in old patients (p < 0.05, ANOVA on ranks).

Figure 3

Apoptosis. A TRAIL expression was immediately significantly reduced in the old patients compared to the healthy control. The reduction in the young patients was significant after surgery but not as distinct as seen in the old patients (p < 0.05, ANOVA on ranks). B FasL was significantly reduced in the young patients after trauma and surgery while no changes could be detected in the old patients (p < 0.05, Anova on ranks).

Figure 4

Neutrophil Apoptosis. Granulocyte apoptosis in the young patients was significantly decreased after trauma and surgery while no changes were detected in old patients compared to healthy controls (p < 0.05, ANOVA on ranks).