title: Immunomodulation by lipid emulsions in pulmonary inflammation: a randomized controlled trial.
abstract: BACKGROUND
  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-α 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.
  
  
  BACKGROUND
  DRKS00006131 at the German Clinical Trial Registry, 2014/05/14.
authors.affiliation: University of Giessen and Marburg Lung Center (UGMLC), Justus-Liebig-University of Giessen, Klinikstr. 33, Giessen, D - 35392, Germany. matthias.hecker@innere.med.uni-giessen.de.
authors.forename: Matthias
authors.initials: M
authors.lastname: Hecker
authors.affiliation: University of Giessen and Marburg Lung Center (UGMLC), Justus-Liebig-University of Giessen, Klinikstr. 33, Giessen, D - 35392, Germany. tomke.linder@googlemail.com.
authors.forename: Tomke
authors.initials: T
authors.lastname: Linder
authors.affiliation: 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.
authors.forename: Juliane
authors.initials: J
authors.lastname: Ott
authors.affiliation: 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.
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Walmrath
authors.affiliation: 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.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Lohmeyer
authors.affiliation: 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.
authors.forename: István
authors.initials: I
authors.lastname: Vadász
authors.affiliation: 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.
authors.forename: Leigh M
authors.initials: LM
authors.lastname: Marsh
authors.affiliation: 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.
authors.forename: Susanne
authors.initials: S
authors.lastname: Herold
authors.affiliation: University of Giessen and Marburg Lung Center (UGMLC), Justus-Liebig-University of Giessen, Klinikstr. 33, Giessen, D - 35392, Germany. martin86reichert@web.de.
authors.forename: Martin
authors.initials: M
authors.lastname: Reichert
authors.affiliation: 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.
authors.forename: Anja
authors.initials: A
authors.lastname: Buchbinder
authors.affiliation: Department of Lung Development and Remodelling, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany. rory.morty@innere.med.uni-giessen.de.
authors.forename: Rory Edward
authors.initials: RE
authors.lastname: Morty
authors.affiliation: University of Giessen and Marburg Lung Center (UGMLC), Justus-Liebig-University of Giessen, Klinikstr. 33, Giessen, D - 35392, Germany. Britta.Bausch@web.de.
authors.forename: Britta
authors.initials: B
authors.lastname: Bausch
authors.affiliation: University of Giessen and Marburg Lung Center (UGMLC), Justus-Liebig-University of Giessen, Klinikstr. 33, Giessen, D - 35392, Germany. tobiasfischer.home@web.de.
authors.forename: Tobias
authors.initials: T
authors.lastname: Fischer
authors.affiliation: 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.
authors.forename: Richard
authors.initials: R
authors.lastname: Schulz
authors.affiliation: 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.
authors.forename: Friedrich
authors.initials: F
authors.lastname: Grimminger
authors.affiliation: Charité - Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Infektiologie und Pneumologie, Berlin, Germany. martin.witzenrath@charite.de.
authors.forename: Martin
authors.initials: M
authors.lastname: Witzenrath
authors.affiliation: Takeda Cambridge Ltd, Cambridge, UK. mbarnes@takedacam.com.
authors.forename: Matt
authors.initials: M
authors.lastname: Barnes
authors.affiliation: 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.
authors.forename: Werner
authors.initials: W
authors.lastname: Seeger
authors.affiliation: 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.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Mayer
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005217:Fat Emulsions, Intravenous / Q000008:administration & dosage*; D005395:Fish Oils / Q000008:administration & dosage; D006801:Humans; D056747:Immunomodulation / Q000187:drug effects* / Q000276:immunology*; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D010865:Pilot Projects; D011014:Pneumonia / Q000188:drug therapy* / Q000276:immunology*; D016037:Single-Blind Method; D013024:Soybean Oil / Q000008:administration & dosage
chemical_list: D005217:Fat Emulsions, Intravenous; D005395:Fish Oils; D018836:Inflammation Mediators; D013024:Soybean Oil