scholarly journals Selective Inhibition of IL-6 Trans-Signaling Has No Beneficial Effect on the Posttraumatic Cytokine Release after Multiple Trauma in Mice

Life ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1252
Author(s):  
Jil-Madeline Homeier ◽  
Katrin Bundkirchen ◽  
Marcel Winkelmann ◽  
Tilman Graulich ◽  
Borna Relja ◽  
...  

While improvements in pre-hospital and in-hospital care allow more multiple trauma patients to advance to intensive care, the incidence of posttraumatic multiple organ dysfunction syndrome (MODS) is on the rise. Herein, the influence of a selective IL-6 trans-signaling inhibition on posttraumatic cytokine levels was investigated as an approach to prevent MODS caused by a dysbalanced posttraumatic immune reaction. Therefore, the artificial IL-6 trans-signaling inhibitor sgp130Fc was deployed in a murine multiple trauma model (femoral fracture plus bilateral chest trauma). The traumatized mice were treated with sgp130Fc (FP) and compared to untreated mice (WT) and IL-6 receptor knockout mice (RKO), which received the same traumas. The overall trauma mortality was 4.4%. Microscopic pulmonary changes were apparent after multiple trauma and after isolated bilateral chest trauma. Elevated IL-6, MCP-3 and RANTES plasma levels were measured after trauma, indicating a successful induction of a systemic inflammatory reaction. Significantly reduced IL-6 and RANTES plasma levels were visible in RKO compared to WT. Only a little effect was visible in FP compared to WT. Comparable cytokine levels in WT and FP indicate neither a protective nor an adverse effect of sgp130Fc on the cytokine release after femoral fracture and bilateral chest trauma.

2018 ◽  
Vol 24 (3) ◽  
pp. 119-123
Author(s):  
Tase Ghinguleac Cristina ◽  
Tudoran Rodica ◽  
Chirila Sergiu ◽  
Gurgas Leonard ◽  
Ion Ileana

Abstract Patients with multiple trauma with thoracic trauma have higher death rates compared to multiple trauma patients without thoracic trauma, mainly because of cardiac injury. We investigated the 24 hours prognostic value of NT-proB-type Natriuretic Peptide (Nt-ProBNP) in polytraumatised patients with thoracic trauma. The study group was composed of 33 patients, 25 males and 8 females. During the study, the endpoint, which was death in the first 24 hours after admission was observed in 33% of the patients (11 patients). Using a cut-off point of 125 pg/ml, the sensitivity of the test was 100% and the specificity was 59.09%. Accoring to the results of the study, NT-ProBNP proves that it might be useful in detecting patients with a bad prognosis, the analyzed enzyme having the capacity of identifying polytrauma patients with thoracic trauma that have high risk of death in the first 24 hours after admission.


2021 ◽  
Vol 26 (1) ◽  
Author(s):  
Julian Haupt ◽  
Niels Krysiak ◽  
Marina Unger ◽  
Viktoria Bogner-Flatz ◽  
Peter Biberthaler ◽  
...  

Abstract 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.


2019 ◽  
Vol 4 (1) ◽  
pp. e000343 ◽  
Author(s):  
Derek JB Kleinveld ◽  
Anita M Tuip-de Boer ◽  
Markus W Hollmann ◽  
Nicole P Juffermans

BackgroundAs a result of improvements in the early resuscitation phase of trauma, mortality is largely driven by later mortality due to multiple organ dysfunction syndrome (MODS), which may be mediated by an early overdrive in the host immune response. If patients at risk for MODS could be identified early, preventive treatment measures could be taken. The aim of this study is to investigate whether specific biomarkers are associated with MODS.MethodsMultiple trauma patients presenting to the Amsterdam University Medical Centers, location Academic Medical Center, between 2012 and 2018 with an Injury Severity Score of 16 or higher were sampled on arrival at the emergency department. A wide variety of inflammatory cytokines, endothelial and lung-specific markers were determined. Comparisons were made between patients with and without MODS. Univariate and multivariate logistic regression was used to determine associations between specific biomarkers and MODS. A p value of 0.05 was considered to be statistically significant.ResultsIn total, 147 multiple trauma patients were included. Of these, 32 patients developed MODS (21.7%). Patients who developed MODS were more severely injured, had more traumatic brain injury and showed more deranged markers of coagulation when compared with patients without MODS. Overall, both proinflammatory and anti-inflammatory cytokines were higher in patients with MODS, indicative of a host immune reaction. In the multivariate analysis, the combination of anti-inflammatory proteins interleukin 1 receptor antagonist (IL-1RA) (OR 1.27 (1.07–1.51), p=0.002) and Clara cell protein 16 (CC-16) (1.06 (1.01–1.05), p=0.031) was most strongly associated with the development MODS.ConclusionsIn trauma, anti-inflammatory proteins IL-1RA and CC-16 have the potential to early identify patients at risk for development of MODS. Further research is warranted to prospectively validate these results.Level of evidencePrognostic study, level III.


2003 ◽  
Vol 20 (10) ◽  
pp. 953-960 ◽  
Author(s):  
Stefan Sauerland ◽  
Thorsten Hensler ◽  
Bertil Bouillon ◽  
Dieter Rixen ◽  
Marcus R. Raum ◽  
...  

2020 ◽  
Author(s):  
Julian Haupt ◽  
Niels Krysiak ◽  
Marina Unger ◽  
Viktoria Bogner-Flatz ◽  
Peter Biberthaler ◽  
...  

Abstract BackgroundMultiple 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.MethodsIn total, 14 multiple trauma patients with an injury severity score (ISS) ³ 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 72h 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. ResultsIn 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. ConclusionsThe results of this study may contribute to identify severely injured patients with a developing SIRS and MOF earlier, in order to adjust therapy strategies.


2016 ◽  
Vol 4 ◽  
pp. 1-7 ◽  
Author(s):  
Ovidiu Horea Bedreag ◽  
Marius Papurica ◽  
Alexandru Florin Rogobete ◽  
Mirela Sarandan ◽  
Carmen Alina Cradigati ◽  
...  

Abstract Nowadays, fluid resuscitation of multiple trauma patients is still a challenging therapy. Existing therapies for volume replacement in severe haemorrhagic shock can lead to adverse reactions that may be fatal for the patient. Patients presenting with multiple trauma often develop hemorrhagic shock, which triggers a series of metabolic, physiological and cellular dysfunction. These disorders combined, lead to complications that significantly decrease survival rate in this subset of patients. Volume and electrolyte resuscitation is challenging due to many factors that overlap. Poor management can lead to post-resuscitation systemic inflammation causing multiple organ failure and ultimately death. In literature, there is no exact formula for this purpose, and opinions are divided. This paper presents a review of modern techniques and current studies regarding the management of fluid resuscitation in trauma patients with hemorrhagic shock. According to the literature and from clinical experience, all aspects regarding post-resuscitation period need to be considered. Also, for every case in particular, emergency therapy management needs to be rigorously respected considering all physiological, biochemical and biological parameters.


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