title: Bioactive products formed in humans from fish oils.
abstract: Resolvins, maresins, and protectins can be formed from fish oils. These specialized pro-resolving mediators (SPMs) have been implicated in the resolution of inflammation. Synthetic versions of such SPMs exert anti-inflammatory effects in vitro and when administered to animal models. However, their importance as endogenous products formed in sufficient amounts to exert anti-inflammatory actions in vivo remains speculative. We biased our ability to detect SPMs formed in healthy volunteers by supplementing fish oil in doses shown previously to influence blood pressure and platelet aggregation under placebo-controlled conditions. Additionally, we sought to determine the relative formation of SPMs during an acute inflammatory response and its resolution, evoked in healthy volunteers by bacterial lipopolysaccharide (LPS). Bioactive lipids, enzymatic epoxyeicosatrienoic acids (EETs), and free radical-catalyzed prostanoids [isoprostanes (iPs)] formed from arachidonic acid and the fish oils, served as comparators. Despite the clear shift from ω-6 to ω-3 EETs and iPs, we failed to detect a consistent signal, in most cases, of SPM formation in urine or plasma in response to fish oil, and in all cases in response to LPS on a background of fish oil. Our results question the relevance of these SPMs to the putative anti-inflammatory effects of fish oils in humans.
authors.affiliation: Institute for Translational Medicine and Therapeutics (ITMAT), Smilow Center for Translational Research, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104.
authors.forename: Carsten
authors.initials: C
authors.lastname: Skarke
authors.affiliation: Institute for Translational Medicine and Therapeutics (ITMAT), Smilow Center for Translational Research, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104.
authors.forename: Naji
authors.initials: N
authors.lastname: Alamuddin
authors.affiliation: Institute for Translational Medicine and Therapeutics (ITMAT), Smilow Center for Translational Research, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104.
authors.forename: John A
authors.initials: JA
authors.lastname: Lawson
authors.affiliation: Institute for Translational Medicine and Therapeutics (ITMAT), Smilow Center for Translational Research, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104.
authors.forename: Xuanwen
authors.initials: X
authors.lastname: Li
authors.affiliation: Institute for Translational Medicine and Therapeutics (ITMAT), Smilow Center for Translational Research, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104.
authors.forename: Jane F
authors.initials: JF
authors.lastname: Ferguson
authors.affiliation: Institute for Translational Medicine and Therapeutics (ITMAT), Smilow Center for Translational Research, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104.
authors.forename: Muredach P
authors.initials: MP
authors.lastname: Reilly
authors.affiliation: Institute for Translational Medicine and Therapeutics (ITMAT), Smilow Center for Translational Research, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104.
authors.forename: Garret A
authors.initials: GA
authors.lastname: FitzGerald
mesh_terms: D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D018957:CD59 Antigens / Q000008:administration & dosage; D019587:Dietary Supplements; D015525:Fatty Acids, Omega-3 / Q000097:blood; D005260:Female; D005395:Fish Oils / Q000008:administration & dosage*; D064368:Healthy Volunteers; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000139:chemically induced / Q000178:diet therapy*; D018836:Inflammation Mediators / Q000097:blood* / Q000138:chemical synthesis; D050356:Lipid Metabolism / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008297:Male
chemical_list: D000893:Anti-Inflammatory Agents; D018957:CD59 Antigens; D015525:Fatty Acids, Omega-3; D005395:Fish Oils; D018836:Inflammation Mediators; D008070:Lipopolysaccharides
keywords: inflammation; lipids; resolution