Ceramide concentrations in septic patients: A possible marker of multiple organ dysfunction syndrome

OBJECTIVES:To investigate the concentrations of mononuclear cell-associated ceramide and serum tumor necrosis factor-α (TNF-α) in patients with sepsis and to assess their predictive value for the development of multiple organ dysfunction syndrome (MODS). DESIGN:Prospective, cohort study. SETTING:Int...

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Veröffentlicht in:Critical care medicine 1999-11, Vol.27 (11), p.2413-2417
Hauptverfasser: Delogu, Giovanna, Famularo, Giuseppe, Amati, Fabrizio, Signore, Luciano, Antonucci, Adriana, Trinchieri, Vito, Di Marzio, Luisa, Cifone, Maria Grazia
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container_end_page 2417
container_issue 11
container_start_page 2413
container_title Critical care medicine
container_volume 27
creator Delogu, Giovanna
Famularo, Giuseppe
Amati, Fabrizio
Signore, Luciano
Antonucci, Adriana
Trinchieri, Vito
Di Marzio, Luisa
Cifone, Maria Grazia
description OBJECTIVES:To investigate the concentrations of mononuclear cell-associated ceramide and serum tumor necrosis factor-α (TNF-α) in patients with sepsis and to assess their predictive value for the development of multiple organ dysfunction syndrome (MODS). DESIGN:Prospective, cohort study. SETTING:Intensive care unit and two research laboratories at a university hospital. PATIENTS:Twenty-three adult patients admitted to an intensive care unit meeting the criteria for diagnosis of sepsis. INTERVENTIONS:Blood samples were collected at the time when diagnosis of sepsis was made. MEASUREMENTS AND MAIN RESULTS:Mononuclear cell-associated ceramide and serum TNF-α were significantly elevated in the samples from the septic patients compared with the control individuals (318.01 ± 270.15 pmol/10 cells vs. 99.90 ± 52.75 pmol/10 cells; p < .001, and 28.52 ± 18.77 pg/mL vs. 10.43 ± 3.37 pg/mL; p < .0001, respectively), and a direct correlation linked ceramide and TNF-α concentrations (r = .90, p < .00001). In the septic patients who went on to develop MODS, ceramide and TNF-α were significantly higher compared with the no MODS patients (489.22 ± 264.93 pmol/10 cells vs. 131.23 ± 99.02 pmol/10 cells; p < .0001, and 40.96 ± 18 pg/mL vs. 14.95 ± 5.60 pg/mL; p < .001, respectively). The receiver operating characteristic curves demonstrated that both TNF-α and ceramide were prognostic of MODS, but ceramide concentrations were more efficient predictors. CONCLUSIONS:These observations suggest that mononuclear cells of peripheral blood from patients with sepsis are committed to undergo apoptosis, because there is evidence that ceramide acts as an endogenous mediator of apoptosis. The strong correlation we found between cell-associated ceramide and serum TNF-α supports the hypothesis that this cytokine plays an important role in activating the sphingomyelin pathway and ceramide generation in patients with sepsis. In addition, this study provides evidence that consistent concentrations of mononuclear cell-associated ceramide may predict progression toward MODS in septic patients.
doi_str_mv 10.1097/00003246-199911000-00015
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DESIGN:Prospective, cohort study. SETTING:Intensive care unit and two research laboratories at a university hospital. PATIENTS:Twenty-three adult patients admitted to an intensive care unit meeting the criteria for diagnosis of sepsis. INTERVENTIONS:Blood samples were collected at the time when diagnosis of sepsis was made. MEASUREMENTS AND MAIN RESULTS:Mononuclear cell-associated ceramide and serum TNF-α were significantly elevated in the samples from the septic patients compared with the control individuals (318.01 ± 270.15 pmol/10 cells vs. 99.90 ± 52.75 pmol/10 cells; p &lt; .001, and 28.52 ± 18.77 pg/mL vs. 10.43 ± 3.37 pg/mL; p &lt; .0001, respectively), and a direct correlation linked ceramide and TNF-α concentrations (r = .90, p &lt; .00001). In the septic patients who went on to develop MODS, ceramide and TNF-α were significantly higher compared with the no MODS patients (489.22 ± 264.93 pmol/10 cells vs. 131.23 ± 99.02 pmol/10 cells; p &lt; .0001, and 40.96 ± 18 pg/mL vs. 14.95 ± 5.60 pg/mL; p &lt; .001, respectively). The receiver operating characteristic curves demonstrated that both TNF-α and ceramide were prognostic of MODS, but ceramide concentrations were more efficient predictors. CONCLUSIONS:These observations suggest that mononuclear cells of peripheral blood from patients with sepsis are committed to undergo apoptosis, because there is evidence that ceramide acts as an endogenous mediator of apoptosis. The strong correlation we found between cell-associated ceramide and serum TNF-α supports the hypothesis that this cytokine plays an important role in activating the sphingomyelin pathway and ceramide generation in patients with sepsis. In addition, this study provides evidence that consistent concentrations of mononuclear cell-associated ceramide may predict progression toward MODS in septic patients.</description><identifier>ISSN: 0090-3493</identifier><identifier>EISSN: 1530-0293</identifier><identifier>DOI: 10.1097/00003246-199911000-00015</identifier><identifier>PMID: 10579257</identifier><identifier>CODEN: CCMDC7</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams &amp; Wilkins, Inc</publisher><subject>Adult ; Aged ; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy ; Apoptosis ; Biological and medical sciences ; Biomarkers - blood ; Ceramides - blood ; Disease Progression ; Emergency and intensive care: infection, septic shock ; Female ; Follow-Up Studies ; Hospitals, University ; Humans ; Intensive care medicine ; Intensive Care Units ; Leukocytes, Mononuclear - metabolism ; Leukocytes, Mononuclear - pathology ; Male ; Medical sciences ; Middle Aged ; Multiple Organ Failure - blood ; Multiple Organ Failure - diagnosis ; Multiple Organ Failure - etiology ; Prognosis ; Prospective Studies ; ROC Curve ; Sepsis - blood ; Sepsis - complications ; Sepsis - diagnosis ; Tumor Necrosis Factor-alpha - metabolism</subject><ispartof>Critical care medicine, 1999-11, Vol.27 (11), p.2413-2417</ispartof><rights>1999 Lippincott Williams &amp; Wilkins, Inc.</rights><rights>2000 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3855-4c9290ea24ffc571a464e97f4fc015f1e7f6ce5570462c4cda06671c988786c63</citedby><cites>FETCH-LOGICAL-c3855-4c9290ea24ffc571a464e97f4fc015f1e7f6ce5570462c4cda06671c988786c63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,27926,27927</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=1222365$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10579257$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Delogu, Giovanna</creatorcontrib><creatorcontrib>Famularo, Giuseppe</creatorcontrib><creatorcontrib>Amati, Fabrizio</creatorcontrib><creatorcontrib>Signore, Luciano</creatorcontrib><creatorcontrib>Antonucci, Adriana</creatorcontrib><creatorcontrib>Trinchieri, Vito</creatorcontrib><creatorcontrib>Di Marzio, Luisa</creatorcontrib><creatorcontrib>Cifone, Maria Grazia</creatorcontrib><title>Ceramide concentrations in septic patients: A possible marker of multiple organ dysfunction syndrome</title><title>Critical care medicine</title><addtitle>Crit Care Med</addtitle><description>OBJECTIVES:To investigate the concentrations of mononuclear cell-associated ceramide and serum tumor necrosis factor-α (TNF-α) in patients with sepsis and to assess their predictive value for the development of multiple organ dysfunction syndrome (MODS). DESIGN:Prospective, cohort study. SETTING:Intensive care unit and two research laboratories at a university hospital. PATIENTS:Twenty-three adult patients admitted to an intensive care unit meeting the criteria for diagnosis of sepsis. INTERVENTIONS:Blood samples were collected at the time when diagnosis of sepsis was made. MEASUREMENTS AND MAIN RESULTS:Mononuclear cell-associated ceramide and serum TNF-α were significantly elevated in the samples from the septic patients compared with the control individuals (318.01 ± 270.15 pmol/10 cells vs. 99.90 ± 52.75 pmol/10 cells; p &lt; .001, and 28.52 ± 18.77 pg/mL vs. 10.43 ± 3.37 pg/mL; p &lt; .0001, respectively), and a direct correlation linked ceramide and TNF-α concentrations (r = .90, p &lt; .00001). In the septic patients who went on to develop MODS, ceramide and TNF-α were significantly higher compared with the no MODS patients (489.22 ± 264.93 pmol/10 cells vs. 131.23 ± 99.02 pmol/10 cells; p &lt; .0001, and 40.96 ± 18 pg/mL vs. 14.95 ± 5.60 pg/mL; p &lt; .001, respectively). The receiver operating characteristic curves demonstrated that both TNF-α and ceramide were prognostic of MODS, but ceramide concentrations were more efficient predictors. CONCLUSIONS:These observations suggest that mononuclear cells of peripheral blood from patients with sepsis are committed to undergo apoptosis, because there is evidence that ceramide acts as an endogenous mediator of apoptosis. The strong correlation we found between cell-associated ceramide and serum TNF-α supports the hypothesis that this cytokine plays an important role in activating the sphingomyelin pathway and ceramide generation in patients with sepsis. In addition, this study provides evidence that consistent concentrations of mononuclear cell-associated ceramide may predict progression toward MODS in septic patients.</description><subject>Adult</subject><subject>Aged</subject><subject>Anesthesia. Intensive care medicine. Transfusions. 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Intensive care medicine. Transfusions. Cell therapy and gene therapy</topic><topic>Apoptosis</topic><topic>Biological and medical sciences</topic><topic>Biomarkers - blood</topic><topic>Ceramides - blood</topic><topic>Disease Progression</topic><topic>Emergency and intensive care: infection, septic shock</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Hospitals, University</topic><topic>Humans</topic><topic>Intensive care medicine</topic><topic>Intensive Care Units</topic><topic>Leukocytes, Mononuclear - metabolism</topic><topic>Leukocytes, Mononuclear - pathology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Multiple Organ Failure - blood</topic><topic>Multiple Organ Failure - diagnosis</topic><topic>Multiple Organ Failure - etiology</topic><topic>Prognosis</topic><topic>Prospective Studies</topic><topic>ROC Curve</topic><topic>Sepsis - blood</topic><topic>Sepsis - complications</topic><topic>Sepsis - diagnosis</topic><topic>Tumor Necrosis Factor-alpha - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Delogu, Giovanna</creatorcontrib><creatorcontrib>Famularo, Giuseppe</creatorcontrib><creatorcontrib>Amati, Fabrizio</creatorcontrib><creatorcontrib>Signore, Luciano</creatorcontrib><creatorcontrib>Antonucci, Adriana</creatorcontrib><creatorcontrib>Trinchieri, Vito</creatorcontrib><creatorcontrib>Di Marzio, Luisa</creatorcontrib><creatorcontrib>Cifone, Maria Grazia</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Critical care medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Delogu, Giovanna</au><au>Famularo, Giuseppe</au><au>Amati, Fabrizio</au><au>Signore, Luciano</au><au>Antonucci, Adriana</au><au>Trinchieri, Vito</au><au>Di Marzio, Luisa</au><au>Cifone, Maria Grazia</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ceramide concentrations in septic patients: A possible marker of multiple organ dysfunction syndrome</atitle><jtitle>Critical care medicine</jtitle><addtitle>Crit Care Med</addtitle><date>1999-11</date><risdate>1999</risdate><volume>27</volume><issue>11</issue><spage>2413</spage><epage>2417</epage><pages>2413-2417</pages><issn>0090-3493</issn><eissn>1530-0293</eissn><coden>CCMDC7</coden><abstract>OBJECTIVES:To investigate the concentrations of mononuclear cell-associated ceramide and serum tumor necrosis factor-α (TNF-α) in patients with sepsis and to assess their predictive value for the development of multiple organ dysfunction syndrome (MODS). DESIGN:Prospective, cohort study. SETTING:Intensive care unit and two research laboratories at a university hospital. PATIENTS:Twenty-three adult patients admitted to an intensive care unit meeting the criteria for diagnosis of sepsis. INTERVENTIONS:Blood samples were collected at the time when diagnosis of sepsis was made. MEASUREMENTS AND MAIN RESULTS:Mononuclear cell-associated ceramide and serum TNF-α were significantly elevated in the samples from the septic patients compared with the control individuals (318.01 ± 270.15 pmol/10 cells vs. 99.90 ± 52.75 pmol/10 cells; p &lt; .001, and 28.52 ± 18.77 pg/mL vs. 10.43 ± 3.37 pg/mL; p &lt; .0001, respectively), and a direct correlation linked ceramide and TNF-α concentrations (r = .90, p &lt; .00001). In the septic patients who went on to develop MODS, ceramide and TNF-α were significantly higher compared with the no MODS patients (489.22 ± 264.93 pmol/10 cells vs. 131.23 ± 99.02 pmol/10 cells; p &lt; .0001, and 40.96 ± 18 pg/mL vs. 14.95 ± 5.60 pg/mL; p &lt; .001, respectively). The receiver operating characteristic curves demonstrated that both TNF-α and ceramide were prognostic of MODS, but ceramide concentrations were more efficient predictors. CONCLUSIONS:These observations suggest that mononuclear cells of peripheral blood from patients with sepsis are committed to undergo apoptosis, because there is evidence that ceramide acts as an endogenous mediator of apoptosis. The strong correlation we found between cell-associated ceramide and serum TNF-α supports the hypothesis that this cytokine plays an important role in activating the sphingomyelin pathway and ceramide generation in patients with sepsis. In addition, this study provides evidence that consistent concentrations of mononuclear cell-associated ceramide may predict progression toward MODS in septic patients.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams &amp; Wilkins, Inc</pub><pmid>10579257</pmid><doi>10.1097/00003246-199911000-00015</doi><tpages>5</tpages></addata></record>
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subjects Adult
Aged
Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy
Apoptosis
Biological and medical sciences
Biomarkers - blood
Ceramides - blood
Disease Progression
Emergency and intensive care: infection, septic shock
Female
Follow-Up Studies
Hospitals, University
Humans
Intensive care medicine
Intensive Care Units
Leukocytes, Mononuclear - metabolism
Leukocytes, Mononuclear - pathology
Male
Medical sciences
Middle Aged
Multiple Organ Failure - blood
Multiple Organ Failure - diagnosis
Multiple Organ Failure - etiology
Prognosis
Prospective Studies
ROC Curve
Sepsis - blood
Sepsis - complications
Sepsis - diagnosis
Tumor Necrosis Factor-alpha - metabolism
title Ceramide concentrations in septic patients: A possible marker of multiple organ dysfunction syndrome
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