title: Oral omega-3 fatty acids promote resolution in chemical peritonitis.
abstract: Recent studies suggest that purified omega-3 fatty acids may attenuate acute inflammation and hasten the transition to healing. In this study, we tested the hypothesis that pretreatment with omega-3-rich fish oil (FO) would promote resolution of peritoneal inflammation through production of specific lipid mediators.
  
  
  
  C57/BL6 mice were given a daily 200-μL oral gavage of saline (CTL) or FO (1.0-1.5 g/kg/d docosahexaenoic acid and 1.3-2.0 g/kg/d eicosapentaenoic acid) for 7 d before chemical peritonitis was induced with thioglycollate. Peritoneal lavage fluid was collected before induction and at days 2 and 4 after peritonitis onset. Prostaglandin E2 (PGE2), Leukotriene B4 (LTB4), Resolvin D1 (RvD1), and the composition of immune cell populations were examined in peritoneal lavage exudates. Cells harvested from the peritoneum were assessed for macrophage differentiation markers, phagocytosis, and lipopolysaccharide-induced cytokine secretion profiles (interleukin [IL]-6, IL-10, IL-1β, TNFα).
  
  
  
  The ratio of RvD1 to pro-inflammatory PGE2 and LTB4 was increased in the peritoneal cavity of FO-supplemented animals. FO induced a decrease in the number of monocytes in the lavage fluid, with no change in the number of macrophages, neutrophils, or lymphocytes. Macrophage phagocytosis and M1/M2 messenger RNA markers were unchanged by FO with the exception of decreased PPARγ expression. FO increased ex vivo TNFα secretion after stimulation with lipopolysaccharide.
  
  
  
  Our findings provide evidence that nutraceutically relevant doses of FO supplements given before and during chemical peritonitis shift the balance of lipid mediators towards a proresolution, anti-inflammatory state without drastically altering the number or phenotype of local innate immune cell populations.
authors.affiliation: Pennsylvania State University College of Medicine, Hershey, Pennsylvania.
authors.forename: Alexander C
authors.initials: AC
authors.lastname: Chacon
authors.affiliation: Department of Surgery, Hershey, Pennsylvania.
authors.forename: Brett E
authors.initials: BE
authors.lastname: Phillips
authors.affiliation: Department of Surgery, Hershey, Pennsylvania.
authors.forename: Miranda A
authors.initials: MA
authors.lastname: Chacon
authors.affiliation: Department of Surgery, Hershey, Pennsylvania.
authors.forename: Deborah
authors.initials: D
authors.lastname: Brunke-Reese
authors.affiliation: Department of Surgery, Hershey, Pennsylvania; Department of Cellular and Molecular Physiology, Hershey, Pennsylvania; Department of Pharmacology, Hershey, Pennsylvania.
authors.forename: Shannon L
authors.initials: SL
authors.lastname: Kelleher
authors.affiliation: Department of Surgery, Hershey, Pennsylvania; Department of Cellular and Molecular Physiology, Hershey, Pennsylvania. Electronic address: dsoybel@hmc.psu.edu.
authors.forename: David I
authors.initials: DI
authors.lastname: Soybel
mesh_terms: D000284:Administration, Oral; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D019587:Dietary Supplements; D004281:Docosahexaenoic Acids / Q000627:therapeutic use*; D015118:Eicosapentaenoic Acid / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010538:Peritonitis / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D013864:Thioglycolates
chemical_list: D015415:Biomarkers; D016207:Cytokines; D013864:Thioglycolates; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid
keywords: Fish oil; Inflammation; Leukotriene B4; Peritonitis; Resolution; Resolvin D1