TY - JOUR
T1 - Danger signals in the ICU
AU - Schenck, Edward J.
AU - Ma, Kevin C.
AU - Murthy, Santosh B.
AU - Choi, Augustine M.K.
N1 - Funding Information:
Supported, in part, by National Institutes of Health grants KL2 TR000458-10 (to Dr. Schenck), R01 HL055330 (to Dr. Choi) and P01 HL108801 (to Dr. Choi).
Funding Information:
1Division of Pulmonary and Critical Care Medicine, Department of Medicine, Weill Cornell Medicine, New York, NY. 2Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pennsylvania, Philadelphia, PA. 3Clinical and Translational Neuroscience Unit, Feil Family Brain and Mind Research Institute, Department of Neurology, Weill Cornell Medicine, New York, NY. Supported, in part, by National Institutes of Health grants KL2 TR000458-10 (to Dr. Schenck), R01 HL055330 (to Dr. Choi) and P01 HL108801 (to Dr. Choi).
Publisher Copyright:
Copyright © 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.
PY - 2018/5/1
Y1 - 2018/5/1
N2 - Objectives: Sterile and infectious critical illnesses often result in vasoplegic shock and a robust systemic inflammatory response that are similar in presentation. The innate immune system is at the center of the response to both infectious and traumatic insults. Damage-associated molecular patterns are small molecules that are released from stressed or dying cells. Damage-associated molecular patterns activate pattern recognition receptors and coordinate the leading edge of the innate immune response. This review introduces the concept of damage-associated molecular patterns and how they activate a systemic inflammatory response, specifically in trauma, neurologic injury, and infection. It also explores how, when carried to extremes, damage-associated molecular patterns may even perpetuate multisystem organ failure. Data Sources: Basic and clinical studies were obtained from a PubMed search through August 2017. Study Selection: Articles considered include original articles, review articles, and conference proceedings. Data Extraction: An analysis of scientific, peer-reviewed data was performed. High quality preclinical and clinical studies adjudicated by the authors were included and summarized. Data Synthesis: Pattern recognition receptors respond to damage-associated molecular patterns and then activate inflammatory pathways. Damage-associated molecular patterns have been linked to the recruitment of sentinel leukocytes and the initiation of the inflammatory cascade. Damage-associated molecular patterns have been linked to many conditions in critical care illnesses. Preclinical models have added insight into how they may mediate distant organ dysfunction. Conclusions: Damage-associated molecular pattern activation and release is an important research for intensive care practitioners. It will add to our understanding of the phase and state of the innate immune response to an insult. Early work is encouraging. However, only with improved understanding of damage-associated molecular pattern activation and function, we can perhaps hope to target damage-associated molecular patterns as diagnostic and/or therapeutic modalities in the future.
AB - Objectives: Sterile and infectious critical illnesses often result in vasoplegic shock and a robust systemic inflammatory response that are similar in presentation. The innate immune system is at the center of the response to both infectious and traumatic insults. Damage-associated molecular patterns are small molecules that are released from stressed or dying cells. Damage-associated molecular patterns activate pattern recognition receptors and coordinate the leading edge of the innate immune response. This review introduces the concept of damage-associated molecular patterns and how they activate a systemic inflammatory response, specifically in trauma, neurologic injury, and infection. It also explores how, when carried to extremes, damage-associated molecular patterns may even perpetuate multisystem organ failure. Data Sources: Basic and clinical studies were obtained from a PubMed search through August 2017. Study Selection: Articles considered include original articles, review articles, and conference proceedings. Data Extraction: An analysis of scientific, peer-reviewed data was performed. High quality preclinical and clinical studies adjudicated by the authors were included and summarized. Data Synthesis: Pattern recognition receptors respond to damage-associated molecular patterns and then activate inflammatory pathways. Damage-associated molecular patterns have been linked to the recruitment of sentinel leukocytes and the initiation of the inflammatory cascade. Damage-associated molecular patterns have been linked to many conditions in critical care illnesses. Preclinical models have added insight into how they may mediate distant organ dysfunction. Conclusions: Damage-associated molecular pattern activation and release is an important research for intensive care practitioners. It will add to our understanding of the phase and state of the innate immune response to an insult. Early work is encouraging. However, only with improved understanding of damage-associated molecular pattern activation and function, we can perhaps hope to target damage-associated molecular patterns as diagnostic and/or therapeutic modalities in the future.
KW - damage-associated molecular patterns
KW - innate immune system
KW - pathogen-associated molecular patterns
KW - sterile systemic inflammatory response
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U2 - 10.1097/CCM.0000000000003007
DO - 10.1097/CCM.0000000000003007
M3 - Review article
C2 - 29443814
AN - SCOPUS:85054135097
VL - 46
SP - 791
EP - 798
JO - Critical Care Medicine
JF - Critical Care Medicine
SN - 0090-3493
IS - 5
ER -