title: Eicosapentaenoic acid suppression of systemic inflammatory responses and inverse up-regulation of 15-deoxyΔ(12,14) prostaglandin J2 production.
abstract: OBJECTIVE
  Eicosapentaenoic acid (EPA) has been shown to suppress immune cell responses, such as cytokine production and downstream PG production in vitro. Studies in vivo, however, have used EPA as a minor constituent of fish oil with variable results. We investigated the effects of EPA on systemic inflammatory responses as pure EPA has not been evaluated on immune/inflammatory responses in vivo.
  
  
  METHODS
  Rabbits were administered polyinosinic: polycytidylic acid (poly I:C) i.v. before and after oral treatment with EPA for 42 days (given daily). The responses to IL-1β and TNF-α were also studied. Immediately following administration of poly I:C, body temperature was continuously monitored and blood samples were taken. Plasma levels of IL-1β, PGE2 (PGE2), and 15-deoxy-Δ(12,14)-PGJ2 (15d-PGJ2) were measured by enzyme immunoassay.
  
  
  RESULTS
  Following EPA treatment, the fever response to poly I:C was markedly suppressed compared with pretreatment responses. This was accompanied by a parallel reduction in the poly I:C-stimulated elevation in plasma levels of IL-1β and PGE2. Paradoxically, the levels of 15d-PGJ2 were higher following EPA treatment. EPA treatment did not significantly alter the fever response or plasma levels of PGE2 in response to either IL-1β or TNF-α.
  
  
  CONCLUSIONS
  Oral treatment with EPA can suppress immune/inflammatory responses in vivo via a suppression of upstream cytokine production resulting in a decreased fever response and indirectly reducing circulating levels of PGE2. EPA also enhances the production of the cytoprotective prostanoid 15d-PGJ2 indicating the therapeutic benefit of EPA.
authors.affiliation: Strathclyde Institute of Pharmacy & Biomedical Sciences, University of Strathclyde, Glasgow, UK.
authors.forename: Jillian
authors.initials: J
authors.lastname: Davidson
authors.forename: Warren
authors.initials: W
authors.lastname: Higgs
authors.forename: Dino
authors.initials: D
authors.lastname: Rotondo
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015118:Eicosapentaenoic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D005334:Fever / Q000097:blood* / Q000139:chemically induced / Q000188:drug therapy; D007155:Immunologic Factors / Q000494:pharmacology* / Q000627:therapeutic use; D053583:Interleukin-1beta / Q000097:blood / Q000494:pharmacology; D011070:Poly I-C; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000097:blood; D011817:Rabbits; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000494:pharmacology
chemical_list: C477819:15-deoxyprostaglandin J2; D000893:Anti-Inflammatory Agents; D007155:Immunologic Factors; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D015118:Eicosapentaenoic Acid; D011070:Poly I-C; D015230:Prostaglandin D2