title: Specialised pro-resolving mediators of inflammation in inflammatory arthritis.
abstract: BACKGROUND
  Specialised pro-resolving mediators (SPM) are derived from n-3 long chain polyunsaturated fatty acids (n-3FA). They promote resolution of inflammation and may contribute to the beneficial effects of n-3FA in patients with arthritis. This study compared SPM in knee effusions and plasma of patients with arthritis taking n-3FA, and plasma of healthy volunteers taking n-3FA.
  
  
  METHODS
  Thirty six patients taking n-3FA undergoing arthrocentesis for an inflammatory knee effusion and 36 healthy volunteers who had taken n-3FA (2.4g/day) for 4 weeks were studied. SPM in synovial fluid and plasma were measured by liquid chromatography-tandem mass spectrometry included 18-hydroxyeicosapentaenoic acid (18-HEPE), the precursor of the E-series SPM (RvE1, RvE2, RvE3, 18R-RvE3), and 17-hydroxydocosahexaenoic acid (17-HDHA), the precursor of the D-series SPM (RvD1, 17R-RvD1, RvD2). Other SPM included protectin D1 (PD1), 10S,17S-dihydroxydocosahexaenoic acid (10,17S-DHDHA), maresin-1 (MaR-1) and 14-hydroxydocosahexaenoic acid (14-HDHA) derived from docosahexaenoic acid (DHA).
  
  
  RESULTS
  E- and D-series SPM and the precursors 18-HEPE and 17-HDHA were present in synovial fluid and plasma of the patients with inflammatory arthritis. Plasma SPM were negatively related to erythrocyte sedimentation rate in arthritis patients (P<0.01) and synovial fluid RvE2 was negatively associated with pain score (P=0.02). Conversion from 18-HEPE and 17-HDHA to E- and D-series SPM was greater in synovial fluid (P<0.01). Most plasma SPM in arthritis patients were elevated (P<0.05) compared with healthy volunteers, and conversion to E- and D-series SPM was greater (P<0.01).
  
  
  CONCLUSIONS
  SPM are present in chronic knee effusions and although the levels are lower than in plasma, the association between synovial fluid RvE2 and reduced pain scores suggests that synthesis of SPM at the site of inflammation is a relevant mechanism by which n-3FA alleviate the symptoms of arthritis.
authors.affiliation: School of Medicine and Pharmacology, Royal Perth Hospital Unit, University of Western Australia, GPO Box X2213, Perth, WA 6847, Australia. Electronic address: anne.barden@uwa.edu.au.
authors.forename: Anne E
authors.initials: AE
authors.lastname: Barden
authors.affiliation: Rheumatology Unit, Royal Adelaide Hospital, North Terrace, Adelaide, SA, Australia; Discipline of Medicine, Adelaide University, Australia.
authors.forename: Mahin
authors.initials: M
authors.lastname: Moghaddami
authors.affiliation: School of Medicine and Pharmacology, Royal Perth Hospital Unit, University of Western Australia, GPO Box X2213, Perth, WA 6847, Australia.
authors.forename: Emilie
authors.initials: E
authors.lastname: Mas
authors.affiliation: Harry Perkins Institute for Medical Research, Perth, WA, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Phillips
authors.affiliation: Rheumatology Unit, Royal Adelaide Hospital, North Terrace, Adelaide, SA, Australia; Discipline of Medicine, Adelaide University, Australia.
authors.forename: Leslie G
authors.initials: LG
authors.lastname: Cleland
authors.affiliation: School of Medicine and Pharmacology, Royal Perth Hospital Unit, University of Western Australia, GPO Box X2213, Perth, WA 6847, Australia.
authors.forename: Trevor A
authors.initials: TA
authors.lastname: Mori
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001168:Arthritis / Q000097:blood* / Q000188:drug therapy; D016022:Case-Control Studies; D019587:Dietary Supplements; D004281:Docosahexaenoic Acids / Q000097:blood*; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D013582:Synovial Fluid / Q000378:metabolism*; D055815:Young Adult
chemical_list: D015525:Fatty Acids, Omega-3; D006893:Hydroxyeicosatetraenoic Acids; C061444:18-hydroxy-5,8,11,14-eicosatetraenoic acid; D004281:Docosahexaenoic Acids; C062894:17-hydroxy-4,7,10,13,15,19-docosahexaenoic acid
keywords: Arthritis; Fish oil; Pain; Resolvins; Specialised pro-resolving mediators; Synovial fluid