Time Course of Plasma Proteomic and Oxylipin Changes Induced by LPS Challenge and Modulated by Antioxidant Supplementation in a Randomized Controlled Trial
Systemic molecular responses to pathogen-associated molecular patterns and their modulation by antioxidants are poorly understood in humans. Here, we present a two-stage clinical interventional study in healthy humans challenged with lipopolysaccharide. In the first step, the kinetics of inflammator...
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2025-04-01
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| Series: | Antioxidants |
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| author | Gerhard Hagn Andrea Bileck Thomas Mohr Doreen Schmidl David M. Baron Bernd Jilma Leopold Schmetterer Gerhard Garhöfer Christopher Gerner |
| author_facet | Gerhard Hagn Andrea Bileck Thomas Mohr Doreen Schmidl David M. Baron Bernd Jilma Leopold Schmetterer Gerhard Garhöfer Christopher Gerner |
| author_sort | Gerhard Hagn |
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| description | Systemic molecular responses to pathogen-associated molecular patterns and their modulation by antioxidants are poorly understood in humans. Here, we present a two-stage clinical interventional study in healthy humans challenged with lipopolysaccharide. In the first step, the kinetics of inflammatory modulators within 8 h were investigated by plasma proteomics and lipidomics. In a second step, the effects of a placebo-controlled antioxidant intervention on the individual responses prior to another lipopolysaccharide challenge were determined. Plasma proteomics revealed an early involvement of the endothelium and platelets, followed by the induction of liver-derived acute phase proteins and an innate immune cell response. Untargeted lipidomics revealed an early release of fatty acids and taurocholic acid, followed by complex regulatory events exerted by oxylipins. The consistent lipopolysaccharide-induced downregulation of lysophospholipids suggested the involvement of the Lands cycle, and the downregulation of deoxycholic acid reinforced emerging links between the inflammasome and bile acids. Groups of molecules with similar kinetics to lipopolysaccharide challenge were observed to share precursors, synthesizing enzymes or cellular origin. Dietary antioxidant supplementation prior to lipopolysaccharide challenge had no detectable effect on protein kinetics but significantly downregulated pro-inflammatory sphingosine-1-phosphate and increased levels of oxylipins, 20-HEPE, and 22-HDoHE, which have been described to facilitate the resolution of inflammation. The present study identified a complex network of lipid mediators deregulated in plasma upon lipopolysaccharide challenge and highlighted the role of platelets, endothelial cells, and erythrocytes as potential inflammatory modulators. While dietary antioxidant supplementation hardly affected the initiation of inflammation, it may exert its effects supporting the resolution of inflammation. |
| format | Article |
| id | doaj-art-e5459674cd424dfcb6db3a02560dee3b |
| institution | OA Journals |
| issn | 2076-3921 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj-art-e5459674cd424dfcb6db3a02560dee3b2025-08-20T02:33:36ZengMDPI AGAntioxidants2076-39212025-04-0114553610.3390/antiox14050536Time Course of Plasma Proteomic and Oxylipin Changes Induced by LPS Challenge and Modulated by Antioxidant Supplementation in a Randomized Controlled TrialGerhard Hagn0Andrea Bileck1Thomas Mohr2Doreen Schmidl3David M. Baron4Bernd Jilma5Leopold Schmetterer6Gerhard Garhöfer7Christopher Gerner8Department of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Waehringer Straße 38, 1090 Vienna, AustriaDepartment of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Waehringer Straße 38, 1090 Vienna, AustriaDepartment of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Waehringer Straße 38, 1090 Vienna, AustriaDepartment of Clinical Pharmacology, Medical University of Vienna, 1090 Vienna, AustriaDepartment of Anaesthesia, Intensive Care Medicine and Pain Medicine, Clinical Division of General Anaesthesia and Intensive Care Medicine, Medical University of Vienna, 1090 Vienna, AustriaDepartment of Clinical Pharmacology, Medical University of Vienna, 1090 Vienna, AustriaDepartment of Clinical Pharmacology, Medical University of Vienna, 1090 Vienna, AustriaDepartment of Clinical Pharmacology, Medical University of Vienna, 1090 Vienna, AustriaDepartment of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Waehringer Straße 38, 1090 Vienna, AustriaSystemic molecular responses to pathogen-associated molecular patterns and their modulation by antioxidants are poorly understood in humans. Here, we present a two-stage clinical interventional study in healthy humans challenged with lipopolysaccharide. In the first step, the kinetics of inflammatory modulators within 8 h were investigated by plasma proteomics and lipidomics. In a second step, the effects of a placebo-controlled antioxidant intervention on the individual responses prior to another lipopolysaccharide challenge were determined. Plasma proteomics revealed an early involvement of the endothelium and platelets, followed by the induction of liver-derived acute phase proteins and an innate immune cell response. Untargeted lipidomics revealed an early release of fatty acids and taurocholic acid, followed by complex regulatory events exerted by oxylipins. The consistent lipopolysaccharide-induced downregulation of lysophospholipids suggested the involvement of the Lands cycle, and the downregulation of deoxycholic acid reinforced emerging links between the inflammasome and bile acids. Groups of molecules with similar kinetics to lipopolysaccharide challenge were observed to share precursors, synthesizing enzymes or cellular origin. Dietary antioxidant supplementation prior to lipopolysaccharide challenge had no detectable effect on protein kinetics but significantly downregulated pro-inflammatory sphingosine-1-phosphate and increased levels of oxylipins, 20-HEPE, and 22-HDoHE, which have been described to facilitate the resolution of inflammation. The present study identified a complex network of lipid mediators deregulated in plasma upon lipopolysaccharide challenge and highlighted the role of platelets, endothelial cells, and erythrocytes as potential inflammatory modulators. While dietary antioxidant supplementation hardly affected the initiation of inflammation, it may exert its effects supporting the resolution of inflammation.https://www.mdpi.com/2076-3921/14/5/536antioxidant supplementationinflammationLands cyclelipidslipopolysaccharideoxylipins |
| spellingShingle | Gerhard Hagn Andrea Bileck Thomas Mohr Doreen Schmidl David M. Baron Bernd Jilma Leopold Schmetterer Gerhard Garhöfer Christopher Gerner Time Course of Plasma Proteomic and Oxylipin Changes Induced by LPS Challenge and Modulated by Antioxidant Supplementation in a Randomized Controlled Trial Antioxidants antioxidant supplementation inflammation Lands cycle lipids lipopolysaccharide oxylipins |
| title | Time Course of Plasma Proteomic and Oxylipin Changes Induced by LPS Challenge and Modulated by Antioxidant Supplementation in a Randomized Controlled Trial |
| title_full | Time Course of Plasma Proteomic and Oxylipin Changes Induced by LPS Challenge and Modulated by Antioxidant Supplementation in a Randomized Controlled Trial |
| title_fullStr | Time Course of Plasma Proteomic and Oxylipin Changes Induced by LPS Challenge and Modulated by Antioxidant Supplementation in a Randomized Controlled Trial |
| title_full_unstemmed | Time Course of Plasma Proteomic and Oxylipin Changes Induced by LPS Challenge and Modulated by Antioxidant Supplementation in a Randomized Controlled Trial |
| title_short | Time Course of Plasma Proteomic and Oxylipin Changes Induced by LPS Challenge and Modulated by Antioxidant Supplementation in a Randomized Controlled Trial |
| title_sort | time course of plasma proteomic and oxylipin changes induced by lps challenge and modulated by antioxidant supplementation in a randomized controlled trial |
| topic | antioxidant supplementation inflammation Lands cycle lipids lipopolysaccharide oxylipins |
| url | https://www.mdpi.com/2076-3921/14/5/536 |
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