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          Institute: MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut)     Collection: Yearbook 2016     Display Documents



ID: 723988.0, MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut) / Yearbook 2016
Immunomodulation by lipid emulsions in pulmonary inflammation: a randomized controlled trial
Authors:Hecker, M.; Linder, T.; Ott, J.; Walmrath, H. D.; Lohmeyer, J.; Vadasz, I.; Marsh, L. M.; Herold, S.; Reichert, M.; Buchbinder, A.; Morty, R. E.; Bausch, B.; Fischer, T.; Schulz, R.; Grimminger, F.; Witzenrath, M.; Barnes, M.; Seeger, W.; Mayer, K.
Date of Publication (YYYY-MM-DD):2015
Title of Journal:Crit Care
Volume:19
Start Page:226
Audience:Not Specified
Abstract / Description:INTRODUCTION: Acute respiratory distress syndrome (ARDS) is a major cause of mortality in intensive care units. As there is rising evidence about immuno-modulatory effects of lipid emulsions required for parenteral nutrition of ARDS patients, we sought to investigate whether infusion of conventional soybean oil (SO)-based or fish oil (FO)-based lipid emulsions rich in either n-6 or n-3 fatty acids, respectively, may influence subsequent pulmonary inflammation. METHODS: In a randomized controlled, single-blinded pilot study, forty-two volunteers received SO, FO, or normal saline for two days. Thereafter, volunteers inhaled pre-defined doses of lipopolysaccharide (LPS) followed by bronchoalveolar lavage (BAL) 8 or 24 h later. In the murine model of LPS-induced lung injury a possible involvement of resolvin E1 (RvE1) receptor ChemR23 was investigated. Wild-type and ChemR23 knockout mice were infused with both lipid emulsions and challenged with LPS intratracheally. RESULTS: In volunteers receiving lipid emulsions, the fatty acid profile in the plasma and in isolated neutrophils and monocytes was significantly changed. Adhesion of isolated monocytes to endothelial cells was enhanced after infusion of SO and reduced by FO, however, no difference of infusion on an array of surface adhesion molecules was detected. In neutrophils and monocytes, LPS-elicited generation of pro-inflammatory cytokines increased in the SO and decreased in the FO group. LPS inhalation in volunteers evoked an increase in neutrophils in BAL fluids, which decreased faster in the FO group. While TNF-alpha in the BAL was increased in the SO group, IL-8 decreased faster in the FO group. In the murine model of lung injury, effects of FO similar to the volunteer group observed in wild-type mice were abrogated in ChemR23 knockout mice. CONCLUSIONS: After infusion of conventional lipid emulsions, leukocytes exhibited increased adhesive and pro-inflammatory features. In contrast, FO-based lipid emulsions reduced monocyte adhesion, decreased pro-inflammatory cytokines, and neutrophil recruitment into the alveolar space possibly mediated by ChemR23-signaling. Lipid emulsions thus exert differential effects in human volunteers and mice in vivo. TRIAL REGISTRATION: DRKS00006131 at the German Clinical Trial Registry, 2014/05/14.
Free Keywords:Animals; Cells, Cultured; Fat Emulsions, Intravenous/*administration & dosage; Fish Oils/administration & dosage; Humans; Immunomodulation/*drug effects/*immunology; Inflammation Mediators/antagonists & inhibitors/immunology; Mice; Mice, Knockout; Pilot Projects; Pneumonia/*drug therapy/*immunology; Single-Blind Method; Soybean Oil/administration & dosage
External Publication Status:published
Document Type:Article
Communicated by:n.n.
Affiliations:MPI für physiologische und klinische Forschung
External Affiliations:University of Giessen and Marburg Lung Center (UGMLC), Justus-Liebig-University of Giessen, Klinikstr. 33, Giessen, D - 35392, Germany. tomke.linder@googlemail.com. University of Giessen and Marburg Lung Center (UGMLC), Justus-Liebig-University of Giessen, Klinikstr. 33, Giessen, D - 35392, Germany. juliane.ott@innere.med.uni-giessen.de. University of Giessen and Marburg Lung Center (UGMLC), Justus-Liebig-University of Giessen, Klinikstr. 33, Giessen, D - 35392, Germany. hans.dieter.walmrath@innere.med.uni-giessen.de. University of Giessen and Marburg Lung Center (UGMLC), Justus-Liebig-University of Giessen, Klinikstr. 33, Giessen, D - 35392, Germany. juergen.lohmeyer@innere.med.uni-giessen.de. University of Giessen and Marburg Lung Center (UGMLC), Justus-Liebig-University of Giessen, Klinikstr. 33, Giessen, D - 35392, Germany. istvan.vadasz@innere.med.uni-giessen.de. University of Giessen and Marburg Lung Center (UGMLC), Justus-Liebig-University of Giessen, Klinikstr. 33, Giessen, D - 35392, Germany. leigh.marsh@lvr.lbg.ac.at. University of Giessen and Marburg Lung Center (UGMLC), Justus-Liebig-University of Giessen, Klinikstr. 33, Giessen, D - 35392, Germany. susanne.herold@innere.med.uni-giessen.de. University of Giessen and Marburg Lung Center (UGMLC), Justus-Liebig-University of Giessen, Klinikstr. 33, Giessen, D - 35392, Germany. martin86reichert@web.de. University of Giessen and Marburg Lung Center (UGMLC), Justus-Liebig-University of Giessen, Klinikstr. 33, Giessen, D - 35392, Germany. anja.buchbinder@innere.med.uni-giessen.de. Department of Lung Development and Remodelling, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany. rory.morty@innere.med.uni-giessen.de. University of Giessen and Marburg Lung Center (UGMLC), Justus-Liebig-University of Giessen, Klinikstr. 33, Giessen, D - 35392, Germany. Britta.Bausch@web.de. University of Giessen and Marburg Lung Center (UGMLC), Justus-Liebig-University of Giessen, Klinikstr. 33, Giessen, D - 35392, Germany. tobiasfischer.home@web.de. University of Giessen and Marburg Lung Center (UGMLC), Justus-Liebig-University of Giessen, Klinikstr. 33, Giessen, D - 35392, Germany. richard.schulz@innere.med.uni-giessen.de. University of Giessen and Marburg Lung Center (UGMLC), Justus-Liebig-University of Giessen, Klinikstr. 33, Giessen, D - 35392, Germany. friedrich.grimminger@innere.med.uni-giessen.de. Charite - Universitatsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Infektiologie und Pneumologie, Berlin, Germany. martin.witzenrath@charite.de. Takeda Cambridge Ltd, Cambridge, UK. mbarnes@takedacam.com. University of Giessen and Marburg Lung Center (UGMLC), Justus-Liebig-University of Giessen, Klinikstr. 33, Giessen, D - 35392, Germany. werner.seeger@innere.med.uni-giessen.de. University of Giessen and Marburg Lung Center (UGMLC), Justus-Liebig-University of Giessen, Klinikstr. 33, Giessen, D - 35392, Germany. konstantin.mayer@innere.med.uni-giessen.de. University of Giessen and Marburg Lung Center (UGMLC), Medical Clinic II, Klinikstr. 33, Giessen, 35392, Germany. konstantin.mayer@innere.med.uni-giessen.de.
Identifiers:ISSN:1466-609X (Electronic) 1364-8535 (Linking) %R 10.1186/s13054-015-0933-6
URL:http://www.ncbi.nlm.nih.gov/pubmed/25962383
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