title: Immune activation by medium-chain triglyceride-containing lipid emulsions is not modulated by n-3 lipids or toll-like receptor 4.
abstract: BACKGROUND
  Saturated medium-chain triglycerides (MCT) as part of the parenteral lipid regimen (50% MCT and 50% long chain triglycerides (LCT)) activate the immune system in vitro. Fish oil (FO)-derived n-3 fatty acids (FA) inhibit saturated FA-induced immune activation via a toll-like receptor (TLR)-4 mediated mechanism. We hypothesized that effects of parenteral MCTs on immune cells involve TLR-4 signaling and that these effects are modulated by n-3 FA that are present in FO.
  
  
  METHODS
  To test this hypothesis we assessed effects of addition of various commercially available mixed parenteral lipid emulsions, n-3 FA and of TLR-4 inhibition on MCT-induced human immune cell activation by evaluation of the expression of leukocyte membrane activation markers and reactive oxygen species (ROS) production.
  
  
  RESULTS
  All MCT-containing lipid emulsions activated leukocytes by inducing changes in expression of membrane markers and stimulus induced ROS production, whereas MCT-free lipid emulsions lacked this effect. Moreover, addition of n-3 FA to LCT/MCT did not prevent MCT-induced immune activation. TLR-4 inhibitors did not distinctly modulate MCT-induced changes in immune function.
  
  
  CONCLUSIONS
  Taken together, these findings suggest that leukocyte activation by parenteral MCTs does not involve TLR-4 signaling and is not modulated by n-3 FA in FO-, but is exerted via different signaling pathways.
authors.affiliation: Intestinal Failure Unit, Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address: Evelyn.Olthof@radboudumc.nl.
authors.forename: Evelyn D
authors.initials: ED
authors.lastname: Olthof
authors.affiliation: Intestinal Failure Unit, Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address: Alexandra.Guelich@gmail.com.
authors.forename: Alexandra F
authors.initials: AF
authors.lastname: Gülich
authors.affiliation: Intestinal Failure Unit, Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands; Membrane Biochemistry & Biophysics, Bijvoet Center for Biomolecular Research and Institute of Biomembranes, Utrecht University, Utrecht, The Netherlands. Electronic address: M.F.Renne@uu.nl.
authors.forename: Mike F
authors.initials: MF
authors.lastname: Renne
authors.affiliation: Intestinal Failure Unit, Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands; Department of Laboratory Medicine - Medical Immunology, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address: Sija.Landman@radboudumc.nl.
authors.forename: Sija
authors.initials: S
authors.lastname: Landman
authors.affiliation: Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address: Leo.Joosten@radboudumc.nl.
authors.forename: Leo A B
authors.initials: LA
authors.lastname: Joosten
authors.affiliation: Intestinal Failure Unit, Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address: Hennie.Roelofs@radboudumc.nl.
authors.forename: Hennie M J
authors.initials: HM
authors.lastname: Roelofs
authors.affiliation: Intestinal Failure Unit, Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address: Geert.Wanten@radboudumc.nl.
authors.forename: Geert J A
authors.initials: GJ
authors.lastname: Wanten
mesh_terms: D004655:Emulsions; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D006801:Humans; D007962:Leukocytes / Q000187:drug effects* / Q000378:metabolism; D008823:Micelles; D017382:Reactive Oxygen Species / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014280:Triglycerides / Q000494:pharmacology*
chemical_list: D004655:Emulsions; D015525:Fatty Acids, Omega-3; D008823:Micelles; D017382:Reactive Oxygen Species; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D014280:Triglycerides
keywords: Fish oil; Immune system; Medium chain triglyceride; Parenteral nutrition; Toll like receptor 4