Hemorrhage is the leading cause of death in severe trauma injuries. When organs or tissues are subjected to prolonged hypoxia, danger signals—known as damage-associated molecular patterns (DAMPs)—are released into the intercellular environment. The endothelium is both the target and a major provider of damage-associated molecular patterns, which are directly involved in immuno-inflammatory dysregulation and the associated tissue suffering. Although damage-associated molecular patterns release begins very early after trauma, this release and its consequences continue beyond the initial treatment. Here we review a few examples of damage-associated molecular patterns to illustrate their pathophysiological roles, with emphasis on emerging therapeutic interventions in the context of severe trauma. Therapeutic intervention administered at precise points during damage-associated molecular patterns release may have beneficial effects by calming the inflammatory storm triggered by traumatic hemorrhagic shock.
Cytokines secreted by individual immune cells regulate tissue regeneration and allow communication between various cell types. Cytokines bind to cognate receptors and trigger the healing process. Determining the orchestration of cytokine interactions with their receptors on their cellular targets is essential to fully understand the process of inflammation and tissue regeneration. To this end, we have investigated the interactions of Interleukin-4 cytokine (IL-4)/Interleukin-4 cytokine receptor (IL-4R) and Interleukin-10 cytokine (IL-10)/Interleukin-10 cytokine receptor (IL-10R) using in situ Proximity Ligation Assays in a regenerative model of skin, muscle and lung tissues in the mini-pig. The pattern of protein-protein interactions was distinct for the two cytokines. IL-4 bound predominantly to receptors on macrophages and endothelial cells around the blood vessels while the target cells of IL-10 were mainly receptors on muscle cells. Our results show that in situ studies of cytokine-receptor interactions can provide unravel the fine details of the mechanism of action of cytokines.
Cytokines secreted by individual immune cells regulate tissue regeneration and allow communication between various cell types. Cytokines bind to cognate receptors and trigger the healing process. Determining the orchestration of cytokine interactions with their receptors on their cellular targets is essential to fully understanding the process of inflammation and tissue regeneration. To this end, we have investigated the interactions of Interleukin-4 cytokine (IL-4)/Interleukin-4 cytokine receptor (IL-4R) and Interleukin-10 cytokine (IL-10)/Interleukin-10 cytokine receptor (IL-10R) using in situ Proximity Ligation Assays in a regenerative model of skin, muscle and lung tissues in the mini-pig. The pattern of protein–protein interactions was distinct for the two cytokines. IL-4 bound predominantly to receptors on macrophages and endothelial cells around the blood vessels while the target cells of IL-10 were mainly receptors on muscle cells. Our results show that in situ studies of cytokine–receptor interactions can unravel the fine details of the mechanism of action of cytokines.
Background: In France, in 2015, prehospital emergency doctors were faced with civilian casualties in hemorrhagic shock resulting from terrorist attacks with automatic rifle fire and explosive weapons. The present study aimed to evaluate the impact of these attacks on the advanced life support (ALS) team’s practices and equipment and on physician training in the prehospital management of traumatic hemorrhagic shock.Methods: This before-and-after multicenter study evaluated professional practices based on a questionnaire sent to emergency department heads and medical practitioners in 370 ALS teams in metropolitan France.Results: We analyzed 672 responses from 209 (56.5 percent) ALS teams in 91 of 95 emergency medical services (EMS) headquarters. Of these 91, 73 (80.2 percent) had a protocol in use for managing traumatic hemorrhagic shock after the attacks, compared with 45 (49.5 percent) who had protocols in use before the attacks (p 0.001). Ultrasound equipment was available in 49 (53.8 percent) of the EMS headquarters after the attacks, compared to 39 (42.9 percent) before (p 0.001). Limb tourniquets were available in 90 (98.9 percent) EMS headquarters after the attacks, versus 27 (29.7 percent) before (p 0.001). Tranexamic acid was available in 88 (96.7 percent) EMS headquarters after the attacks, versus 71 (78 percent) before (p 0.001). During the post-attack period, training in war medicine did not affect individual practices, neither for using the shock index or the Focused Assessment with Sonography for Trauma (FAST) nor the tourniquet. However, this training was associated with more frequent use of hemostatic dressings (p = 0.002).Conclusion: Following the attacks in Paris and Nice, ALS teams received additional equipment and training to prepare for future mass causality events.
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