Trauma Severity and Its Impact on Local Inflammation in Extremity Injury—Insights From a Combined Trauma Model in Pigs

Abstract

Background: Extremity fracture is frequently seen in multiple traumatized patients. Local post-traumatic inflammatory reactions as well as local and systemic interactions have been described in previous studies. However, trauma severity and its impact on the local immunologic reaction remains unclear. Therefore, fracture-associated local inflammation was investigated in a porcine model of isolated and combined trauma to gain information about the early inflammatory stages. Material and Methods: Polytrauma (PT) consisted of lung contusion, liver laceration, femur fracture, and controlled hemorrhage. Monotrauma (MT) consisted of femur fracture only. The fracture was operatively stabilized and animals were monitored under ICU-standard for 72 h. Blood, fracture hematoma (FH) as well as muscle samples were collected throughout the experimental period. Levels of local and systemic pro-and anti-inflammatory as well as angiogenetic cytokines were measured by ELISA. Results: Both groups showed a significant decrease in pro-inflammatory IL-6 in FH over time. However, concentrations in MT were significantly higher than in PT. The IL-8 concentrations initially decreased in FH, but recovered by the end of the observation period. These dynamics were only statistically significant in MT. Furthermore, concentrations measured in muscle tissue showed inverse kinetics compared to those in FH. The IL-10 did not present statistical resilient dynamics over time, although a slight increase in FH was seen by the end of the observation time in the MT group. Conclusions: Time-dependent dynamics of the local inflammatory response were observed. Trauma severity showed a significant impact, with lower values in pro-as well as angiogenetic mediators. Fracture repair could be altered by these trauma-related changes of the local immunologic milieu, which might serve as a possible explanation for the higher rates of delayed or non-union bone repair in polytraumatised patients.

Fracture Fixation Strategy and Specific Muscle Tissue Availability of Neutrophilic Granulocytes Following Mono- and Polytrauma: Intramedullary Nailing Vs. External Fixation of Femoral Fractures

“…Muscle tissue provides bones with oxygen, nutrients, and osteoprogenitor cells, but it also seems critical for bone healing due to its immunological potential. In this context, the humeral response in the musculature has been shown to be in uenced by trauma severity and by the strategy used for fracture xation, indicating a potential effect of muscle on the early phase of fracture healing [18]. In the current study, we focused on changes in PMNL in ltration to assess the cellular aspects of the muscular immune response and to elucidate the role of both concomitant injuries and the strategy of fracture xation in a translationally relevant, long-term pig model.…”

Fracture fixation strategy and specific muscle tissue availability of neutrophilic granulocytes following mono- and polytrauma: intramedullary nailing vs. external fixation of femoral fractures

“…Muscle tissue provides bones with oxygen, nutrients, and osteoprogenitor cells, but it also seems critical for bone healing due to its immunological potential. In this context, the humeral response in the musculature has been shown to be in uenced by trauma severity and by the strategy used for fracture xation, indicating a potential effect of muscle on the early phase of fracture healing [11]. In the current study, we focused on changes in PMNL in ltration to assess the cellular aspects of the muscular immune response and to elucidate the role of both concomitant injuries and the strategy of fracture xation in a translationally relevant, long-term pig model.…”

“…Nevertheless, for fracture hematoma it was shown that it might have different cytokine patterns then other fracture surrounding tissues and thus also different cellular compositions than those in the muscle tissue [11]. Consequently, in addition to the musculature, the fracture hematoma and maybe additional soft tissues are also of particular importance for trauma outcome.…”

Low-Dose IL-34 Has No Effect on Osteoclastogenesis But Promotes Osteogenesis of Hbmscs Partly Via Activation of The PI3K/AKT And ERK Signaling Pathways 

“…During fracture healing, the local fracture hematoma at a fracture site is rich in multiple cytokines, in ammatory factors, and many kinds of cells, which are helpful for bone and soft tissue repair [6]. Horst et al [7] pointed out that there was evidential up-regulation of the concentrations of interleukin-6 (IL -6) and interleukin-8 (IL-8) in fracture hematomas when compared with the serum values in a combined trauma pig model. According to previous studies, IL-6 and IL-8 obviously affect the osteoblastogenesis and osteoclastogenesis [7][8][9][10].…”

“…Horst et al [7] pointed out that there was evidential up-regulation of the concentrations of interleukin-6 (IL -6) and interleukin-8 (IL-8) in fracture hematomas when compared with the serum values in a combined trauma pig model. According to previous studies, IL-6 and IL-8 obviously affect the osteoblastogenesis and osteoclastogenesis [7][8][9][10]. Interleukin-34 (IL-34), a newly discovered cytokine, showing capable of inducing pro-in ammatory cytokines and chemokines such as IL-6 and IL-8 [11].…”