Analysis of fatty acid-derived lipids in critically ill patients after cardiac surgery yields novel pathophysiologically relevant mediators with possible relevance for systemic inflammatory reactions
IntroductionCritically ill patients suffer from a wide variety of clinical events, most of them leading to pro-inflammatory states such as sepsis or simply as consequence of major surgery. Many of these patients develop forms of acute kidney injury, heart or acute liver failure during intensive care...
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Frontiers Media S.A.
2025-01-01
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| author | Holger Neb Verena Roth Jessica Roos Jessica Roos Tom Bauer Anja Urbschat Ulrike Heinicke Carlo Angioni Dieter Steinhilber Dieter Steinhilber Matthias Piesche Matthias Piesche Nerea Ferreirós Robert Gurke Robert Gurke Gerd Geisslinger Gerd Geisslinger Edith Utech Kai Zacharowski Patrick Meybohm Patrick Meybohm Patrick Paulus Elke Schmitt Elke Schmitt Thorsten Jürgen Maier Thorsten Jürgen Maier |
| author_facet | Holger Neb Verena Roth Jessica Roos Jessica Roos Tom Bauer Anja Urbschat Ulrike Heinicke Carlo Angioni Dieter Steinhilber Dieter Steinhilber Matthias Piesche Matthias Piesche Nerea Ferreirós Robert Gurke Robert Gurke Gerd Geisslinger Gerd Geisslinger Edith Utech Kai Zacharowski Patrick Meybohm Patrick Meybohm Patrick Paulus Elke Schmitt Elke Schmitt Thorsten Jürgen Maier Thorsten Jürgen Maier |
| author_sort | Holger Neb |
| collection | DOAJ |
| description | IntroductionCritically ill patients suffer from a wide variety of clinical events, most of them leading to pro-inflammatory states such as sepsis or simply as consequence of major surgery. Many of these patients develop forms of acute kidney injury, heart or acute liver failure during intensive care. Lipid signaling is critically involved in triggering systemic inflammation processes, pain and vascular tone. We therefore hypothesized that fatty-acid-derived lipid mediators might be regulated during inflammatory stages and other clinical events in critically ill patients and might serve as potential biomarker candidates.Methods and study designUsing liquid chromatography-tandem mass spectrometry (LC-MS/MS), we determined the levels of 53 lipid mediators in plasma from nine patients. These patients were hospitalized at Frankfurt University Hospital’s intensive care unit (ICU) after cardiac surgery. Inflammatory stages were illustrated over time using clinically established biomarkers such as interleukin-6 (IL-6) and leukocyte count. Normal range values of the lipids were obtained from healthy volunteers.ResultsPlasma levels clearly outside the normal range were observed for 22 of 53 lipid mediators, of which 13 were increased (including ceramides Cer (d18:0/18:0), Cer (d18:1/16:0), Cer (d18:1/18:1), glucosyl-ceramide GluCer (d18:1/24:1), lactosylceramide LacCer (d18:1/18:0), and LacCer (d18:1/24:1), 6-keto-prostaglandin F1alpha (6-keto-PGF1alpha), 11,12- and 14,15-DHET and 1- and 2-arachidonoyl glycerol (1-AG and 2-AG), Sphingosine SPH (d18:1) and 20-HETE. Furthermore, nine lipids were decreased (Cer (d18:1/24:0), LacCer (d18:1/16:0), LacCer (d18:1/24:0), sphingosine-1-phosphate S1P (d18:1), S1P (d18:0), the lysophosphatidic acids LPA (16:0), LPA (18:0), LPA (18:1) and 9-HODE. Among increased lipids, the remarkable changes in 1-AG, 2-AG, and to a lower extent of 6-keto-PGF1-alpha plasma levels showed a certain agreement with inflammatory phases. Furthermore, 6-keto-PGF1alpha had its peak shortly before initiation of continuous veno-venous hemodialysis (at least in 5 of the observed patients), 2-AG was elevated in all our nine patients during (right) heart failure in the context of either re-opening patient’s chest, implementation of veno-arterial ECMO or at least while significantly increasing the amount of catecholamines.DiscussionIn this pilot trial we identified several evaluated lipids in critically ill patients representing either potentially (patho-) physiologically relevant mediators of the pro-inflammatory processes and during heart failure or possible markers preceding veno-venous hemodialysis. |
| format | Article |
| id | doaj-art-9527ed5dfc4943aabd89984ad0e01d84 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-9527ed5dfc4943aabd89984ad0e01d842025-01-31T13:43:01ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011510.3389/fimmu.2024.11488061148806Analysis of fatty acid-derived lipids in critically ill patients after cardiac surgery yields novel pathophysiologically relevant mediators with possible relevance for systemic inflammatory reactionsHolger Neb0Verena Roth1Jessica Roos2Jessica Roos3Tom Bauer4Anja Urbschat5Ulrike Heinicke6Carlo Angioni7Dieter Steinhilber8Dieter Steinhilber9Matthias Piesche10Matthias Piesche11Nerea Ferreirós12Robert Gurke13Robert Gurke14Gerd Geisslinger15Gerd Geisslinger16Edith Utech17Kai Zacharowski18Patrick Meybohm19Patrick Meybohm20Patrick Paulus21Elke Schmitt22Elke Schmitt23Thorsten Jürgen Maier24Thorsten Jürgen Maier25Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, Frankfurt University Hospital, Goethe University Frankfurt, Frankfurt, GermanyDepartment of Immunology, Paul-Ehrlich-Institute (Federal Institute for Vaccines and Biomedicines), Langen, GermanyDepartment of Anesthesiology, Intensive Care Medicine and Pain Therapy, Frankfurt University Hospital, Goethe University Frankfurt, Frankfurt, GermanyDepartment of Immunology, Paul-Ehrlich-Institute (Federal Institute for Vaccines and Biomedicines), Langen, GermanyDepartment of Immunology, Paul-Ehrlich-Institute (Federal Institute for Vaccines and Biomedicines), Langen, GermanyDepartment of Biomedicine, Aarhus University, Aarhus, DenmarkDepartment of Anesthesiology, Intensive Care Medicine and Pain Therapy, Frankfurt University Hospital, Goethe University Frankfurt, Frankfurt, GermanyInstitute of Clinical Pharmacology, Frankfurt University Hospital, Frankfurt, GermanyInstitute of Pharmaceutical Chemistry, Goethe University Frankfurt, Frankfurt, GermanyFraunhofer Institute for Translational Medicine and Pharmacology (ITMP) and Fraunhofer Cluster of Excellence for Immune Mediated Diseases (CIMD), Frankfurt, GermanyBiomedical Research Laboratories, Medicine Faculty, Universidad Católica del Maule, Talca, ChileOncology Center, Medicine Faculty, Universidad Católica del Maule, Talca, ChileInstitute of Clinical Pharmacology, Frankfurt University Hospital, Frankfurt, GermanyInstitute of Clinical Pharmacology, Frankfurt University Hospital, Frankfurt, GermanyFraunhofer Institute for Translational Medicine and Pharmacology (ITMP) and Fraunhofer Cluster of Excellence for Immune Mediated Diseases (CIMD), Frankfurt, GermanyInstitute of Clinical Pharmacology, Frankfurt University Hospital, Frankfurt, GermanyFraunhofer Institute for Translational Medicine and Pharmacology (ITMP) and Fraunhofer Cluster of Excellence for Immune Mediated Diseases (CIMD), Frankfurt, GermanyDepartment of Anesthesiology, Intensive Care Medicine and Pain Therapy, Frankfurt University Hospital, Goethe University Frankfurt, Frankfurt, GermanyDepartment of Anesthesiology, Intensive Care Medicine and Pain Therapy, Frankfurt University Hospital, Goethe University Frankfurt, Frankfurt, GermanyDepartment of Anesthesiology, Intensive Care Medicine and Pain Therapy, Frankfurt University Hospital, Goethe University Frankfurt, Frankfurt, GermanyDepartment of Anesthesiology, Intensive Care, Emergency and Pain Medicine University Hospital Wuerzburg, Wuerzburg, Germany0Laboratory for Experimental Anesthesiology, Johannes Kepler University (JKU), Linz, Austria, Department of Anesthesiology and Operative Intensive Care Medicine, Kepler University Hospital Linz, Linz, AustriaDepartment of Anesthesiology, Intensive Care Medicine and Pain Therapy, Frankfurt University Hospital, Goethe University Frankfurt, Frankfurt, Germany1Institute of Biostatistics and Mathematical Modelling, Department of Medicine, Goethe University Frankfurt, Frankfurt, GermanyDepartment of Anesthesiology, Intensive Care Medicine and Pain Therapy, Frankfurt University Hospital, Goethe University Frankfurt, Frankfurt, GermanyDepartment of Immunology, Paul-Ehrlich-Institute (Federal Institute for Vaccines and Biomedicines), Langen, GermanyIntroductionCritically ill patients suffer from a wide variety of clinical events, most of them leading to pro-inflammatory states such as sepsis or simply as consequence of major surgery. Many of these patients develop forms of acute kidney injury, heart or acute liver failure during intensive care. Lipid signaling is critically involved in triggering systemic inflammation processes, pain and vascular tone. We therefore hypothesized that fatty-acid-derived lipid mediators might be regulated during inflammatory stages and other clinical events in critically ill patients and might serve as potential biomarker candidates.Methods and study designUsing liquid chromatography-tandem mass spectrometry (LC-MS/MS), we determined the levels of 53 lipid mediators in plasma from nine patients. These patients were hospitalized at Frankfurt University Hospital’s intensive care unit (ICU) after cardiac surgery. Inflammatory stages were illustrated over time using clinically established biomarkers such as interleukin-6 (IL-6) and leukocyte count. Normal range values of the lipids were obtained from healthy volunteers.ResultsPlasma levels clearly outside the normal range were observed for 22 of 53 lipid mediators, of which 13 were increased (including ceramides Cer (d18:0/18:0), Cer (d18:1/16:0), Cer (d18:1/18:1), glucosyl-ceramide GluCer (d18:1/24:1), lactosylceramide LacCer (d18:1/18:0), and LacCer (d18:1/24:1), 6-keto-prostaglandin F1alpha (6-keto-PGF1alpha), 11,12- and 14,15-DHET and 1- and 2-arachidonoyl glycerol (1-AG and 2-AG), Sphingosine SPH (d18:1) and 20-HETE. Furthermore, nine lipids were decreased (Cer (d18:1/24:0), LacCer (d18:1/16:0), LacCer (d18:1/24:0), sphingosine-1-phosphate S1P (d18:1), S1P (d18:0), the lysophosphatidic acids LPA (16:0), LPA (18:0), LPA (18:1) and 9-HODE. Among increased lipids, the remarkable changes in 1-AG, 2-AG, and to a lower extent of 6-keto-PGF1-alpha plasma levels showed a certain agreement with inflammatory phases. Furthermore, 6-keto-PGF1alpha had its peak shortly before initiation of continuous veno-venous hemodialysis (at least in 5 of the observed patients), 2-AG was elevated in all our nine patients during (right) heart failure in the context of either re-opening patient’s chest, implementation of veno-arterial ECMO or at least while significantly increasing the amount of catecholamines.DiscussionIn this pilot trial we identified several evaluated lipids in critically ill patients representing either potentially (patho-) physiologically relevant mediators of the pro-inflammatory processes and during heart failure or possible markers preceding veno-venous hemodialysis.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1148806/fulleicosanoidsprostaglandinssphingolipidsceramidesendocannabinoidssystemic inflammation |
| spellingShingle | Holger Neb Verena Roth Jessica Roos Jessica Roos Tom Bauer Anja Urbschat Ulrike Heinicke Carlo Angioni Dieter Steinhilber Dieter Steinhilber Matthias Piesche Matthias Piesche Nerea Ferreirós Robert Gurke Robert Gurke Gerd Geisslinger Gerd Geisslinger Edith Utech Kai Zacharowski Patrick Meybohm Patrick Meybohm Patrick Paulus Elke Schmitt Elke Schmitt Thorsten Jürgen Maier Thorsten Jürgen Maier Analysis of fatty acid-derived lipids in critically ill patients after cardiac surgery yields novel pathophysiologically relevant mediators with possible relevance for systemic inflammatory reactions Frontiers in Immunology eicosanoids prostaglandins sphingolipids ceramides endocannabinoids systemic inflammation |
| title | Analysis of fatty acid-derived lipids in critically ill patients after cardiac surgery yields novel pathophysiologically relevant mediators with possible relevance for systemic inflammatory reactions |
| title_full | Analysis of fatty acid-derived lipids in critically ill patients after cardiac surgery yields novel pathophysiologically relevant mediators with possible relevance for systemic inflammatory reactions |
| title_fullStr | Analysis of fatty acid-derived lipids in critically ill patients after cardiac surgery yields novel pathophysiologically relevant mediators with possible relevance for systemic inflammatory reactions |
| title_full_unstemmed | Analysis of fatty acid-derived lipids in critically ill patients after cardiac surgery yields novel pathophysiologically relevant mediators with possible relevance for systemic inflammatory reactions |
| title_short | Analysis of fatty acid-derived lipids in critically ill patients after cardiac surgery yields novel pathophysiologically relevant mediators with possible relevance for systemic inflammatory reactions |
| title_sort | analysis of fatty acid derived lipids in critically ill patients after cardiac surgery yields novel pathophysiologically relevant mediators with possible relevance for systemic inflammatory reactions |
| topic | eicosanoids prostaglandins sphingolipids ceramides endocannabinoids systemic inflammation |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1148806/full |
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