Are Pentraxin 3 and Transsignaling Early Markers for Immunologic Injury Severity in Polytrauma? A Pilot Study

Abstract

Background Inflammatory-related conditions and organ failure (OF) lead to late trauma mortality. Cytokine profiles can predict adverse events and mortality, potentially guiding treatment strategies (damage control surgery versus early total care). However, the specific cytokines to predict the clinical course in polytraumatized patients are not fully identified. Questions/purposes We investigated the early pentraxin 3 (PTX3), IL-6, soluble IL-6 receptor (sIL-6R), and transsignaling ratio (TSR) in polytraumatized patients to estimate immunologic injury severity and predict OF and survival. Methods We prospectively followed 58 patients with severe polytrauma, six patients with minor trauma, and 10 healthy volunteers. The mean Injury Severity Score (ISS) was 43 points and the mean Hannover Polytrauma Score (PTS) was 59 points, with a consequently high mortality rate (30%). Twenty-seven of the 58 polytraumatized patients (46%) developed OF, 67% systemic inflammatory response syndrome, and 38% sepsis. Results Mean sIL-6R concentrations in polytrauma initially were low. Mean PTX3 concentrations were high and peaked at 24 hours. The mean TSR peaked at 6 hours; at that time, the mean value was higher for nonsurvivors. PTX3 concentrations at admission were associated with injury severity calculated by ISS and PTS. Higher PTX3 serum concentrations 24 hours after admission correlated with lower probability for survival. Conclusions PTX3, sIL-6R, and TSR were early markers for posttraumatic inflammatory status, OF, injury severity, and TSR for survival after polytrauma. The temporal profile of PTX3 and TSR might be used to anticipate the total injury severity and the clinical course and thereby guide decision making in polytraumatized patients. Level of Evidence Level II, prognostic study. See Instructions for Authors for a complete description of levels of evidence.

Temporal profile of inflammatory response to fracture and hemorrhagic shock: Proposal of a novel long-term survival murine multiple trauma model

“…Most of the deaths occurred within 24–72 h but no clear description of survival period and mortality rate was given. Analogue to our clinical pilot study we analyzed the posttraumatic IL‐6 and transsignaling mechanism in our murine multiple trauma model to characterize the posttraumatic immune response in our model. We observed analogue peak values and kinetics of IL‐6, sIL‐6R and TSR compared to our human pilot study .…”

“…The interactions of hemorrhagic shock and bone healing have attracted major interest known to exert profound impact on the clinical course and outcome of multiple trauma patients . Depending on the trauma severity the above mentioned scenario of inflammatory derangements is typically associated with an enhanced systemic proinflammatory cytokine response, such as an increase in Interleukin 6 (IL‐6) level and decrease in soluble IL‐6 receptor (sIL‐6R), associated with multiple organ failure, systemic inflammatory response syndrome and sepsis . IL‐6 in turn was demonstrated to exert accelerating effects on callus formation and bone healing and is essential during the early phase of bone healing as it initiates immune signaling at the fracture hematoma .…”

“…Although IL‐6 has been evaluated as a possible marker to measure posttraumatic immune response, other studies have used gene expression arrays to estimate the inflammatory response and predict SIRS and Sepsis . In a pilot study we were able to demonstrate that a transsignaling mechanism driven by the agonistic soluble IL‐6 cytokine receptor (sIL‐6R) was associated with a marked proinflammatory posttraumatic immune response, predisposing for organ failure and decreased survival . Unfortunately, fundamental pathophysiologic regulatory mechanisms relating posttraumatic immune response to bone healing processes are still unknown.…”

Assessment of Severity and Prognosis of Polytrauma Outcome: the Current State of the Problem (Review)

“…The prospects of various immune reaction markers (sIL-6R, pentraxin 3) [76], IL-1β, IL-8, IL-10 [77] for evaluating severity and predicting complications and outcome in polytrauma are emphasized, but they are inaccessible for assessment and included in no evaluation scale.…”

Editorial Comment: Symposium: Tscherne Festschrift: Editorial Comment

“…Sturm, Pape (Fig. 2), and Dienstknecht [5] provide an overarching view in a paper examining the political, economic, and medical factors underlying trauma systems in Germany and North America. Dienstknecht et al [1] examine potential factors for predicting complications with extremity trauma surgery.…”