Eicosapentaenoic acid suppression of systemic inflammatory responses and inverse up-regulation of 15-deoxy Δ12,14 Prostaglandin J2 production

Davidson, Jillian and Higgs, Warren and Rotondo, D (2013) Eicosapentaenoic acid suppression of systemic inflammatory responses and inverse up-regulation of 15-deoxy Δ12,14 Prostaglandin J2 production. British Journal of Pharmacology, 169 (5). pp. 1130-1139. ISSN 1476-5381

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Abstract

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. 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. 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. 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.