title: Sepsis-associated changes of the arachidonic acid metabolism and their diagnostic potential in septic patients.
abstract: OBJECTIVE
  Sepsis-associated changes of the arachidonic acid metabolism and the utility of arachidonic acid metabolites for the diagnosis of sepsis have been poorly investigated so far. Therefore, the primary objective of our study was to screen for differentially regulated arachidonic acid metabolites in septic patients using a lipopolysaccharide whole-blood model and to investigate their diagnostic potential.
  
  
  METHODS
  Prospective, observational, single-center, clinical study.
  
  
  METHODS
  Intensive care unit at University Hospital Leipzig.
  
  
  METHODS
  Thirty-five patients (first cohort 25 patients, second cohort 10 patients) meeting the criteria for severe sepsis or septic shock were enrolled. Eighteen healthy volunteers (first cohort 15 subjects, second cohort 3 subjects) were enrolled as controls.
  
  
  METHODS
  None.
  
  
  RESULTS
  Arachidonic acid and its metabolites were investigated in supernatants of nonactivated (baseline) and lipopolysaccharide-activated heparinized whole blood of healthy subjects (n=15) and septic patients (n=25) by solid phase extraction and subsequent liquid chromatography-tandem mass spectrometry. Arachidonic acid, arachidonic acid analogues, and the cyclooxygenase-associated metabolites prostaglandin E2, 11-hydroxyeicosatetraenoic acid, and thromboxane B2 were identified as differentiating metabolites between septic patients and healthy subjects. Some of these compounds, including arachidonic acid, its analogues, and the cyclooxygenase metabolites prostaglandin E2 and thromboxane B2 differed at baseline. The inducibility of arachidonic acid and the cyclooxygenase metabolites 11-hydroxyeicosatetraenoic and prostaglandin E2 were reduced by 80% to 90% in septic patients. The degree of the inducibility was associated with severity of sepsis and clinical outcome. A reduced inducibility of COX-2 but preserved inducibility of mPGES-1 on gene expression level were confirmed in an independent cohort of septic patients (n=10) by quantitative reverse-transcription polymerase chain reaction compared to healthy controls (n=3).
  
  
  CONCLUSIONS
  Arachidonic acid metabolism is markedly affected in patients with sepsis. Our data suggest that the analysis of arachidonic acid metabolites in an in vitro whole blood activation model may be a promising approach for risk estimation in septic patients that has to be further evaluated in subsequent large-scale clinical studies.
authors.affiliation: Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, Department of Internal Medicine, Intensive Care Unit, University Hospital Leipzig, Leipzig, Germany. Mathias.Bruegel@med.uni-muenchen.de
authors.forename: Mathias
authors.initials: M
authors.lastname: Bruegel
authors.forename: Ute
authors.initials: U
authors.lastname: Ludwig
authors.forename: Alisa
authors.initials: A
authors.lastname: Kleinhempel
authors.forename: Sirak
authors.initials: S
authors.lastname: Petros
authors.forename: Linda
authors.initials: L
authors.lastname: Kortz
authors.forename: Uta
authors.initials: U
authors.lastname: Ceglarek
authors.forename: Lesca Miriam
authors.initials: LM
authors.lastname: Holdt
authors.forename: Joachim
authors.initials: J
authors.lastname: Thiery
authors.forename: Georg Martin
authors.initials: GM
authors.lastname: Fiedler
mesh_terms: D000328:Adult; D000368:Aged; D016718:Arachidonic Acid / Q000097:blood / Q000378:metabolism*; D002853:Chromatography, Liquid; D015232:Dinoprostone / Q000097:blood; D005260:Female; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000097:blood; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018805:Sepsis / Q000097:blood / Q000175:diagnosis / Q000378:metabolism*; D012772:Shock, Septic / Q000097:blood / Q000175:diagnosis / Q000378:metabolism; D053719:Tandem Mass Spectrometry; D013929:Thromboxane B2 / Q000097:blood; D055815:Young Adult
chemical_list: D006893:Hydroxyeicosatetraenoic Acids; D016718:Arachidonic Acid; D013929:Thromboxane B2; C027356:11-hydroxy-5,8,12,14-eicosatetraenoic acid; D015232:Dinoprostone