The potential of adipokines in identifying multiple trauma patients at risk of developing multiple organ dysfunction syndrome.

BACKGROUND: Multiple organ dysfunction syndrome (MODS) and the consecutive multiple organ failure (MOF) are severe and dreaded complications with a high mortality in multiple trauma patients. The aim of this study was to investigate the potential of the adipokines leptin, resistin, interleukin-17A and interleukin-33 as possible biomarkers in the early posttraumatic inflammatory response and for identifying severely traumatized patients at risk of developing MODS. METHODS: In total, 14 multiple trauma patients with an injury severity score (ISS) ≥ 16 as well as a control group of 14 non-multiple trauma patients were included in this study and blood samples were taken at the time points 0, 6, 24, 48 and 72 h after admission. For the trauma patients, the SIRS and Denver MOF score were determined daily. The quantitative measurement of the plasma concentrations of the adipokines was performed using ELISA. RESULTS: In the statistical analysis, the multiple trauma patients showed statistically significant higher plasma concentrations of leptin, resistin, IL-17A and IL-33 compared to the control group. In addition, there was a statistically significant positive correlation between the concentrations of resistin, IL-17A and IL-33 and the corresponding SIRS scores and between the concentrations of resistin, IL-17A and IL-33 and the corresponding Denver MOF scores. Finally, ROC curve analysis revealed that the adipokines leptin and IL-17A are suitable diagnostic markers for the discrimination between multiple trauma patients with and without MOF. CONCLUSIONS: Leptin and IL-17A could be suitable diagnostic markers to identify severely injured patients with a developing SIRS and MOF earlier, to adjust surgical therapy planning and intensive care.

Trauma Induces Interleukin-17A Expression on Th17 Cells and CD4+ Regulatory T Cells as Well as Platelet Dysfunction.

Background: The organism's immune response to trauma is distinctively controlled, its dysregulation leading to severe post-traumatic complications. Platelets, CD4+ regulatory T cells (CD4+ Tregs) and T helper 17 (Th17) cells have been identified to participate in the post-traumatic immune response. Unfortunately, little is known about their exact role and potential interdependency in humans. Aims of this clinical trial were to phenotype the human immune response following injury and to identify risk factors rendering the host more susceptible to trauma induced injury. Methods: This non-interventional prospective clinical trial enrolled patients following multiple trauma, follow up was conducted for 10 days. Peripheral blood CD4+ Tregs and Th17 cells were analyzed using flow cytometry to determine Interleukin 17A (IL-17A) expression. Hemostasis and platelet function were assessed with rotational thromboelastometry (ROTEM®). Subgroup analysis was conducted for the factors gender, age, and trauma severity. Results and Conclusion: This is the first clinical trial to phenotype the immune response following trauma, focusing on platelets, and the adaptive immune response. We discovered a novel increased IL-17A expression on Th17 cells and on CD4+ Tregs following trauma and describe the kinetics of the immune response. The IL-17A response on CD4+ Tregs challenges the ascribed role of CD4+ Tregs to be solely counter inflammatory in this setting. Furthermore, despite a rising number of platelets, ROTEM analysis shows post-traumatic platelet dysfunction. Subgroup analysis revealed gender, age, and trauma severity as influencing factors for several of the analyzed parameters.