title: The Nociceptin/Orphanin FQ system is modulated in patients admitted to ICU with sepsis and after cardiopulmonary bypass.
abstract: OBJECTIVE
  Nociceptin/Orphanin FQ (N/OFQ) is a non-classical endogenous opioid peptide that modulates immune function in vitro. Its importance in inflammation and human sepsis is unknown. The objectives of this study were to determine the relationship between N/OFQ, transcripts for its precursor (pre-pro-N/OFQ [ppNOC]) and receptor (NOP), inflammatory markers and clinical outcomes in patients undergoing cardiopulmonary bypass and with sepsis.
  
  
  METHODS
  A prospective observational cohort study of 82 patients admitted to Intensive Care (ICU) with sepsis and 40 patients undergoing cardiac surgery under cardiopulmonary bypass (as a model of systemic inflammation). Sixty three healthy volunteers, matched by age and sex to the patients with sepsis were also studied. Clinical and laboratory details were recorded. Polymorph ppNOC and NOP receptor mRNA were determined using quantitative PCR. Plasma N/OFQ was determined using ELISA and cytokines (TNF- α, IL-8, IL-10) measured using radioimmunoassay. Data from patients undergoing cardiac surgery were recorded before, 3 and 24 hours after cardiopulmonary bypass. ICU patients with sepsis were assessed on Days 1 and 2 of ICU admission, and after clinical recovery.
  
  
  RESULTS
  Plasma N/OFQ concentrations increased (p<0.0001) on Days 1 and 2 of ICU admission with sepsis compared to matched recovery samples. Polymorph ppNOC (p= 0.019) and NOP mRNA (p<0.0001) decreased compared to healthy volunteers. TNF-α, IL-8 and IL-10 concentrations increased on Day 1 compared to matched recovery samples and volunteers (p<0.0001). Similar changes (increased plasma N/OFQ, [p=0.0058], decreased ppNOC [p<0.0001], increased IL-8 and IL-10 concentrations [both p<0.0001]) occurred after cardiac surgery but these were comparatively lower and of shorter duration.
  
  
  CONCLUSIONS
  The N/OFQ system is modulated in ICU patients with sepsis with similar but reduced changes after cardiac surgery under cardiopulmonary bypass. Further studies are required to clarify the role of the N/OFQ system in inflammation and sepsis, and the mechanisms involved.
authors.affiliation: Division of Anaesthesia, Critical Care and Pain Management, Department of Cardiovascular Sciences, University of Leicester, Leicester Royal Infirmary, Leicester, United Kingdom.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Thompson
authors.forename: Alcira
authors.initials: A
authors.lastname: Serrano-Gomez
authors.forename: John
authors.initials: J
authors.lastname: McDonald
authors.forename: Nadia
authors.initials: N
authors.lastname: Ladak
authors.forename: Sarah
authors.initials: S
authors.lastname: Bowrey
authors.forename: David G
authors.initials: DG
authors.lastname: Lambert
mesh_terms: D000368:Aged; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D016022:Case-Control Studies; D003422:Critical Care; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D018847:Opioid Peptides / Q000235:genetics / Q000378:metabolism*; D011183:Postoperative Complications; D012333:RNA, Messenger / Q000235:genetics; D011957:Receptors, Opioid / Q000235:genetics / Q000378:metabolism; D018805:Sepsis / Q000209:etiology* / Q000378:metabolism* / Q000628:therapy; D013997:Time Factors; D000097629:Nociceptin
chemical_list: D016207:Cytokines; D018847:Opioid Peptides; D012333:RNA, Messenger; D011957:Receptors, Opioid; D000097629:Nociceptin