Premium
Eicosapentaenoic acid suppression of systemic inflammatory responses and inverse up‐regulation of 15‐deoxyΔ 12,14 P rostaglandin J 2 production
Author(s) -
Davidson Jillian,
Higgs Warren,
Rotondo Dino
Publication year - 2013
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.12209
Subject(s) - eicosapentaenoic acid , in vivo , cytokine , immune system , ex vivo , chemistry , tumor necrosis factor alpha , fish oil , medicine , endocrinology , lipopolysaccharide , pharmacology , inflammation , immunology , in vitro , biology , biochemistry , fatty acid , polyunsaturated fatty acid , microbiology and biotechnology , fishery , fish <actinopterygii>
Background and Purpose 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 . Experimental Approach 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, PG E 2 ( PGE 2 ), and 15‐deoxy‐Δ 12,14 ‐ PGJ 2 ( 15d‐PGJ 2 ) were measured by enzyme immunoassay. Key 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 PGE 2 . Paradoxically, the levels of 15d‐ PGJ 2 were higher following EPA treatment. EPA treatment did not significantly alter the fever response or plasma levels of PGE 2 in response to either IL ‐1β or TNF ‐α. Conclusion and Implications 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 PGE 2 . EPA also enhances the production of the cytoprotective prostanoid 15d‐ PGJ 2 indicating the therapeutic benefit of EPA .