Postinjury Inflammation and Organ Dysfunction

Sauaia, Angela; Moore, Frederick A.; Moore, Ernest E.

doi:10.1016/j.ccc.2016.08.006

Cited by 138 publications

(133 citation statements)

References 148 publications

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“…This disruption constitutes the beginning of a rapidly activated innate immune response 1 that aims to end the dangerous situation for the recipient of the traumatic insult but can also result in severe complications and death 2–5 . The innate immune response after severe tissue trauma or life-threatening multiple injury (polytrauma) results in a multi-faceted systemic disease with a complex and heterogeneous, although mainly compartmentalized, response 6–8 .…”

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confidence: 99%

Innate immune responses to trauma

2018

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Trauma can affect any individual at any location and at any time over a lifespan. The disruption of macrobarriers and microbarriers induces instant activation of innate immunity. The subsequent complex response, designed to limit further damage and induce healing, also represents a major driver of complications and fatal outcome after injury. This Review aims to provide basic concepts about the posttraumatic response and is focused on the interactive events of innate immunity at frequent sites of injury: the endothelium at large, and sites within the lungs, inside and outside the brain and at the gut barrier.

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confidence: 99%

Innate immune responses to trauma

2018

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“…Nowadays, CARS is not regarded as part of a biphasic inflammatory response consisting of an initial SIRS with a subsequent CARS. It became evident that the hyper-resolving processes of inflammation (CARS, IS) occur nearly in parallel with the hyperinflammatory response, but also that they can exist separately from the SIRS [28,59]. Moreover, CARS is not only a simplified anti-inflammatory process, but rather a disorder caused by a hyper-resolution of inflammation.…”

Section: Cars and Sampsmentioning

confidence: 99%

Damage-associated molecular patterns in trauma

Relja

Land

2019

Eur J Trauma Emerg Surg

131

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In 1994, the "danger model" argued that adaptive immune responses are driven rather by molecules released upon tissue damage than by the recognition of "strange" molecules. Thus, an alternative to the "self versus non-self recognition model" has been provided. The model, which suggests that the immune system discriminates dangerous from safe molecules, has established the basis for the future designation of damage-associated molecular patterns (DAMPs), a term that was coined by Walter G. Land, Seong, and Matzinger. The pathological importance of DAMPs is barely somewhere else evident as in the posttraumatic or post-surgical inflammation and regeneration. Since DAMPs have been identified to trigger specific immune responses and inflammation, which is not necessarily detrimental but also regenerative, it still remains difficult to describe their "friend or foe" role in the posttraumatic immunogenicity and healing process. DAMPs can be used as biomarkers to indicate and/or to monitor a disease or injury severity, but they also may serve as clinically applicable parameters for optimized indication of the timing for, i.e., secondary surgeries. While experimental studies allow the detection of these biomarkers on different levels including cellular, tissue, and circulatory milieu, this is not always easily transferable to the human situation. Thus, in this review, we focus on the recent literature dealing with the pathophysiological importance of DAMPs after traumatic injury. Since dysregulated inflammation in traumatized patients always implies disturbed resolution of inflammation, so-called model of suppressing/inhibiting inducible DAMPs (SAMPs) will be very briefly introduced. Thus, an update on this topic in the field of trauma will be provided.

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“…Indications for which SAMPs may be chosen as therapeutic targets may be situations such as unwanted hyperresolution and/or immunosuppression, for example, those observed in compensatory anti-inflammatory response syndrome (CARS) following polytrauma [63]. Again, when choosing SAMPs as therapeutic targets, they should be druggable molecules.…”

Section: Damps and Samps As Therapeutic Targetsmentioning

confidence: 99%

Use of DAMPs and SAMPs as Therapeutic Targets or Therapeutics: A Note of Caution

Land

2020

Mol Diagn Ther

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This opinion article discusses the increasing attention paid to the role of activating damage-associated molecular patterns (DAMPs) in initiation of inflammatory diseases and suppressing/inhibiting DAMPs (SAMPs) in resolution of inflammatory diseases and, consequently, to the future roles of these novel biomarkers as therapeutic targets and therapeutics. Since controlled production of DAMPs and SAMPs is needed to achieve full homeostatic restoration and repair from tissue injury, only their pathological, not their homeostatic, concentrations should be therapeutically tackled. Therefore, distinct caveats are proposed regarding choosing DAMPs and SAMPs for therapeutic purposes. For example, we discuss the need to a priori identify and define a context-dependent "homeostatic DAMP:SAMP ratio" in each case and a "homeostatic window" of DAMP and SAMP concentrations to guarantee a safe treatment modality to patients. Finally, a few clinical examples of how DAMPs and SAMPs might be used as therapeutic targets or therapeutics in the future are discussed, including inhibition of DAMPs in hyperinflammatory processes (e.g., systemic inflammatory response syndrome, as currently observed in , administration of SAMPs in chronic inflammatory diseases, inhibition of SAMPs in hyperresolving processes (e.g., compensatory antiinflammatory response syndrome), and administration/induction of DAMPs in vaccination procedures and anti-cancer therapy.

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Postinjury Inflammation and Organ Dysfunction

Cited by 138 publications

References 148 publications

Innate immune responses to trauma

Innate immune responses to trauma

Damage-associated molecular patterns in trauma

Use of DAMPs and SAMPs as Therapeutic Targets or Therapeutics: A Note of Caution

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