The Nociceptin/Orphanin FQ system is modulated in patients admitted to ICU with sepsis and after cardiopulmonary bypass

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...

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Veröffentlicht in:PloS one 2013-10, Vol.8 (10), p.e76682-e76682
Hauptverfasser: Thompson, Jonathan P, Serrano-Gomez, Alcira, McDonald, John, Ladak, Nadia, Bowrey, Sarah, Lambert, David G
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Serrano-Gomez, Alcira
McDonald, John
Ladak, Nadia
Bowrey, Sarah
Lambert, David G
description 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. 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. Plasma N/OFQ concentrations increased (p
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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. 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. Plasma N/OFQ concentrations increased (p&lt;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&lt;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&lt;0.0001). Similar changes (increased plasma N/OFQ, [p=0.0058], decreased ppNOC [p&lt;0.0001], increased IL-8 and IL-10 concentrations [both p&lt;0.0001]) occurred after cardiac surgery but these were comparatively lower and of shorter duration. 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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0076682</identifier><identifier>PMID: 24124588</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Aged ; Bypasses ; Cardiopulmonary Bypass - adverse effects ; Case-Control Studies ; Coronary artery bypass ; Critical Care ; Cytokines ; Cytokines - blood ; Cytokines - metabolism ; Enzyme-linked immunosorbent assay ; Female ; Gene Expression Regulation ; Heart ; Heart diseases ; Heart surgery ; Histamine ; Hospital patients ; Humans ; Hypotheses ; Immune response ; Infection ; Infections ; Inflammation ; Intensive care ; Intensive Care Units ; Interleukin 10 ; Interleukin 8 ; Lymphocytes ; Male ; Medical research ; Medicine ; Middle Aged ; Mortality ; Narcotics ; Nociceptin ; Observational studies ; Opioid Peptides - genetics ; Opioid Peptides - metabolism ; Opioids ; Pain management ; Patients ; Peptides ; Postoperative Complications ; Radioimmunoassay ; Receptors, Opioid - genetics ; Receptors, Opioid - metabolism ; Recovery ; RNA ; RNA, Messenger - genetics ; Sepsis ; Sepsis - etiology ; Sepsis - metabolism ; Sepsis - therapy ; Surgery ; Thompson, David ; Time Factors ; Tumor necrosis factor-TNF ; Tumor necrosis factor-α</subject><ispartof>PloS one, 2013-10, Vol.8 (10), p.e76682-e76682</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 Thompson et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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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. 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. Plasma N/OFQ concentrations increased (p&lt;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&lt;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&lt;0.0001). Similar changes (increased plasma N/OFQ, [p=0.0058], decreased ppNOC [p&lt;0.0001], increased IL-8 and IL-10 concentrations [both p&lt;0.0001]) occurred after cardiac surgery but these were comparatively lower and of shorter duration. 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.</description><subject>Aged</subject><subject>Bypasses</subject><subject>Cardiopulmonary Bypass - adverse effects</subject><subject>Case-Control Studies</subject><subject>Coronary artery bypass</subject><subject>Critical Care</subject><subject>Cytokines</subject><subject>Cytokines - blood</subject><subject>Cytokines - metabolism</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>Female</subject><subject>Gene Expression Regulation</subject><subject>Heart</subject><subject>Heart diseases</subject><subject>Heart surgery</subject><subject>Histamine</subject><subject>Hospital patients</subject><subject>Humans</subject><subject>Hypotheses</subject><subject>Immune response</subject><subject>Infection</subject><subject>Infections</subject><subject>Inflammation</subject><subject>Intensive care</subject><subject>Intensive Care Units</subject><subject>Interleukin 10</subject><subject>Interleukin 8</subject><subject>Lymphocytes</subject><subject>Male</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Middle Aged</subject><subject>Mortality</subject><subject>Narcotics</subject><subject>Nociceptin</subject><subject>Observational studies</subject><subject>Opioid Peptides - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Thompson, Jonathan P</au><au>Serrano-Gomez, Alcira</au><au>McDonald, John</au><au>Ladak, Nadia</au><au>Bowrey, Sarah</au><au>Lambert, David G</au><au>Bueno, Valquiria</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Nociceptin/Orphanin FQ system is modulated in patients admitted to ICU with sepsis and after cardiopulmonary bypass</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2013-10-04</date><risdate>2013</risdate><volume>8</volume><issue>10</issue><spage>e76682</spage><epage>e76682</epage><pages>e76682-e76682</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>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. 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. Plasma N/OFQ concentrations increased (p&lt;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&lt;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&lt;0.0001). Similar changes (increased plasma N/OFQ, [p=0.0058], decreased ppNOC [p&lt;0.0001], increased IL-8 and IL-10 concentrations [both p&lt;0.0001]) occurred after cardiac surgery but these were comparatively lower and of shorter duration. 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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24124588</pmid><doi>10.1371/journal.pone.0076682</doi><tpages>e76682</tpages><oa>free_for_read</oa></addata></record>
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subjects Aged
Bypasses
Cardiopulmonary Bypass - adverse effects
Case-Control Studies
Coronary artery bypass
Critical Care
Cytokines
Cytokines - blood
Cytokines - metabolism
Enzyme-linked immunosorbent assay
Female
Gene Expression Regulation
Heart
Heart diseases
Heart surgery
Histamine
Hospital patients
Humans
Hypotheses
Immune response
Infection
Infections
Inflammation
Intensive care
Intensive Care Units
Interleukin 10
Interleukin 8
Lymphocytes
Male
Medical research
Medicine
Middle Aged
Mortality
Narcotics
Nociceptin
Observational studies
Opioid Peptides - genetics
Opioid Peptides - metabolism
Opioids
Pain management
Patients
Peptides
Postoperative Complications
Radioimmunoassay
Receptors, Opioid - genetics
Receptors, Opioid - metabolism
Recovery
RNA
RNA, Messenger - genetics
Sepsis
Sepsis - etiology
Sepsis - metabolism
Sepsis - therapy
Surgery
Thompson, David
Time Factors
Tumor necrosis factor-TNF
Tumor necrosis factor-α
title The Nociceptin/Orphanin FQ system is modulated in patients admitted to ICU with sepsis and after cardiopulmonary bypass
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