Human Sepsis Eicosanoid and Proresolving Lipid Mediator Temporal Profiles: Correlations With Survival and Clinical Outcomes

To identify and measure recently described chemical mediators, termed specialized pro-resolving mediators that actively regulate the resolution of acute-inflammation, and correlate measurements with clinical outcomes. Herein, deidentified plasma was collected from sepsis patients (n = 22 subjects) w...

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Published inCritical care medicine Vol. 45; no. 1; p. 58
Main Authors Dalli, Jesmond, Colas, Romain A, Quintana, Carolina, Barragan-Bradford, Diana, Hurwitz, Shelley, Levy, Bruce D, Choi, Augustine M, Serhan, Charles N, Baron, Rebecca M
Format Journal Article
LanguageEnglish
Published United States 01.01.2017
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Abstract To identify and measure recently described chemical mediators, termed specialized pro-resolving mediators that actively regulate the resolution of acute-inflammation, and correlate measurements with clinical outcomes. Herein, deidentified plasma was collected from sepsis patients (n = 22 subjects) within 48 hours of admission to the ICU and on days 3 and 7 thereafter and subjected to lipid mediator profiling. Brigham and Women's Hospital Medical Intensive Care Unit. Patients in the medical ICU with sepsis. In all patients, we identified more than 30 bioactive mediators and pathway markers in peripheral blood using established criteria for arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid metabolomes. These included inflammation initiating mediators leukotriene B4 and prostaglandin E2 and pro-resolving mediators resolvin D1, resolvin D2, and protectin D1. In sepsis nonsurvivors, we found significantly higher inflammation-initiating mediators including prostaglandin F2α and leukotriene B4 and pro-resolving mediators, including resolvin E1, resolvin D5, and 17R-protectin D1 than was observed in surviving sepsis subjects. This signature was present at ICU admission and persisted for 7 days. Further analysis revealed increased respiratory failure in nonsurvivors. Higher inflammation-initiating mediators (including prostaglandin F2α) and select proresolving pathways were associated with the development of acute respiratory distress syndrome, whereas other traditional clinical indices were not predictive of acute respiratory distress syndrome development. These results provide peripheral blood lipid mediator profiles in sepsis that correlate with survival and acute respiratory distress syndrome development, thus suggesting plausible novel biomarkers and biologic targets for critical illness.
AbstractList To identify and measure recently described chemical mediators, termed specialized pro-resolving mediators that actively regulate the resolution of acute-inflammation, and correlate measurements with clinical outcomes. Herein, deidentified plasma was collected from sepsis patients (n = 22 subjects) within 48 hours of admission to the ICU and on days 3 and 7 thereafter and subjected to lipid mediator profiling. Brigham and Women's Hospital Medical Intensive Care Unit. Patients in the medical ICU with sepsis. In all patients, we identified more than 30 bioactive mediators and pathway markers in peripheral blood using established criteria for arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid metabolomes. These included inflammation initiating mediators leukotriene B4 and prostaglandin E2 and pro-resolving mediators resolvin D1, resolvin D2, and protectin D1. In sepsis nonsurvivors, we found significantly higher inflammation-initiating mediators including prostaglandin F2α and leukotriene B4 and pro-resolving mediators, including resolvin E1, resolvin D5, and 17R-protectin D1 than was observed in surviving sepsis subjects. This signature was present at ICU admission and persisted for 7 days. Further analysis revealed increased respiratory failure in nonsurvivors. Higher inflammation-initiating mediators (including prostaglandin F2α) and select proresolving pathways were associated with the development of acute respiratory distress syndrome, whereas other traditional clinical indices were not predictive of acute respiratory distress syndrome development. These results provide peripheral blood lipid mediator profiles in sepsis that correlate with survival and acute respiratory distress syndrome development, thus suggesting plausible novel biomarkers and biologic targets for critical illness.
Author Quintana, Carolina
Baron, Rebecca M
Dalli, Jesmond
Levy, Bruce D
Barragan-Bradford, Diana
Serhan, Charles N
Hurwitz, Shelley
Colas, Romain A
Choi, Augustine M
Author_xml – sequence: 1
  givenname: Jesmond
  surname: Dalli
  fullname: Dalli, Jesmond
  organization: 1Center for Experimental Therapeutics and Reperfusion Injury, Harvard Institutes of Medicine, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. 2Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. 3Center for Clinical Investigation, Brigham and Women's Hospital and Harvard Medical School, Boston, MA
– sequence: 2
  givenname: Romain A
  surname: Colas
  fullname: Colas, Romain A
– sequence: 3
  givenname: Carolina
  surname: Quintana
  fullname: Quintana, Carolina
– sequence: 4
  givenname: Diana
  surname: Barragan-Bradford
  fullname: Barragan-Bradford, Diana
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  givenname: Shelley
  surname: Hurwitz
  fullname: Hurwitz, Shelley
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  givenname: Bruce D
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  fullname: Serhan, Charles N
– sequence: 9
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  fullname: Baron, Rebecca M
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Snippet To identify and measure recently described chemical mediators, termed specialized pro-resolving mediators that actively regulate the resolution of...
SourceID pubmed
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StartPage 58
SubjectTerms Adult
Aged
Aged, 80 and over
Bicarbonates - blood
Bilirubin - blood
Blood Gas Analysis
Cytokines - blood
Discriminant Analysis
Docosahexaenoic Acids - blood
Eicosanoids - blood
Female
Glasgow Coma Scale
Humans
Intensive Care Units
Male
Massachusetts - epidemiology
Middle Aged
Partial Thromboplastin Time
Respiration, Artificial - statistics & numerical data
Respiratory Distress Syndrome, Adult - blood
Respiratory Distress Syndrome, Adult - etiology
Respiratory Insufficiency - mortality
Sepsis - blood
Sepsis - mortality
Vasoconstrictor Agents - therapeutic use
Title Human Sepsis Eicosanoid and Proresolving Lipid Mediator Temporal Profiles: Correlations With Survival and Clinical Outcomes
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