Eicosapentaenoic acid suppression of systemic inflammatory responses and inverse up‐regulation of 15‐deoxyΔ 12,14 P rostaglandin J 2 production

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 .