title: Human Sepsis Eicosanoid and Proresolving Lipid Mediator Temporal Profiles: Correlations With Survival and Clinical Outcomes.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  Brigham and Women's Hospital Medical Intensive Care Unit.
  
  
  METHODS
  Patients in the medical ICU with sepsis.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Jesmond
authors.initials: J
authors.lastname: Dalli
authors.forename: Romain A
authors.initials: RA
authors.lastname: Colas
authors.forename: Carolina
authors.initials: C
authors.lastname: Quintana
authors.forename: Diana
authors.initials: D
authors.lastname: Barragan-Bradford
authors.forename: Shelley
authors.initials: S
authors.lastname: Hurwitz
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Levy
authors.forename: Augustine M
authors.initials: AM
authors.lastname: Choi
authors.forename: Charles N
authors.initials: CN
authors.lastname: Serhan
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Baron
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001639:Bicarbonates / Q000097:blood; D001663:Bilirubin / Q000097:blood; D001784:Blood Gas Analysis; D016207:Cytokines / Q000097:blood; D016002:Discriminant Analysis; D004281:Docosahexaenoic Acids / Q000097:blood*; D015777:Eicosanoids / Q000097:blood*; D005260:Female; D015600:Glasgow Coma Scale; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008404:Massachusetts / Q000453:epidemiology; D008875:Middle Aged; D010314:Partial Thromboplastin Time; D012121:Respiration, Artificial / Q000706:statistics & numerical data; D012128:Respiratory Distress Syndrome / Q000097:blood / Q000209:etiology; D012131:Respiratory Insufficiency / Q000401:mortality*; D018805:Sepsis / Q000097:blood* / Q000401:mortality*; D014662:Vasoconstrictor Agents / Q000627:therapeutic use
chemical_list: D001639:Bicarbonates; D016207:Cytokines; D015777:Eicosanoids; D014662:Vasoconstrictor Agents; D004281:Docosahexaenoic Acids; D001663:Bilirubin