title: Omega-3 fatty acid lipid emulsion reduces LPS-stimulated macrophage TNF-alpha production.
abstract: BACKGROUND
  Omega-3 (omega-3) fatty acids (FA), specifically eicosapentaenoic acid (EPA), attenuate cytokine-mediated inflammation. Currently, in the United States, there is no commercial source of omega-3 lipid for clinical use. A clinically used European lipid emulsion, Omegaven, has been shown to have beneficial antiinflammatory effects; however, the mechanisms of its action are not well defined. In the present work, this omega-3 FA emulsion has been evaluated in order to define its effects on TNF-alpha production in a model of LPS-stimulated macrophages.
  
  
  METHODS
  RAW 264.7 cells (1 x 10(6) cell/well) were incubated with DMEM, Omegaven, or an isoenergetic omega-6 lipid emulsion, Lipovenos for 4 h. Cells were washed and then stimulated with LPS (1 microg/mL) or media alone for 3 h. Plate well supernatants were collected and assayed for TNF-alpha production by ELISA. Statistical analysis was performed by ANOVA and post-hoc analyses; the significance was defined as p < 0.05.
  
  
  RESULTS
  Unstimulated RAW cell TNF-alpha production was similar in all groups and < 60 pg/mL. Lipovenos pretreatment did not alter TNF-alpha production from that of baseline compared to LPS-stimulated cells. Four-hour Omegaven pretreatment significantly reduced TNF-alpha production in LPS-stimulated cells, with a 46% reduction in TNF-alpha from baseline observed.
  
  
  CONCLUSIONS
  Four-hour omega-3 FA emulsion pretreatment significantly attenuated LPS-stimulated macrophage TNF-alpha production. These data support the contention that antiinflammatory effects of omega-3 FA occur at least in part through the inhibition of macrophage TNF-alpha production in response to endotoxin. Further studies to define the antiinflammatory mechanisms of omega-3 FA on macrophages are warranted. The availability of Omegaven as an experimental treatment and Lipovenos as an equivalent control will be useful for future studies.
authors.affiliation: Department of Surgery, University of Illinois at Chicago, 840 South Wood Street, Chicago, IL 60612, USA.
authors.forename: Tricia A
authors.initials: TA
authors.lastname: Babcock
authors.forename: W Scott
authors.initials: WS
authors.lastname: Helton
authors.forename: David
authors.initials: D
authors.lastname: Hong
authors.forename: N Joseph
authors.initials: NJ
authors.lastname: Espat
mesh_terms: D000818:Animals; D002460:Cell Line; D015118:Eicosapentaenoic Acid / Q000276:immunology / Q000494:pharmacology; D004655:Emulsions / Q000494:pharmacology; D004731:Endotoxins; D015525:Fatty Acids, Omega-3 / Q000276:immunology / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated / Q000276:immunology / Q000494:pharmacology; D008070:Lipopolysaccharides; D008213:Lymphocyte Activation; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology*; D051379:Mice; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000276:immunology
chemical_list: D004655:Emulsions; D004731:Endotoxins; D015525:Fatty Acids, Omega-3; D005231:Fatty Acids, Unsaturated; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D015118:Eicosapentaenoic Acid