Davidson Jillian, Higgs Warren, Rotondo Dino
Strathclyde Institute of Pharmacy & Biomedical Sciences, University of Strathclyde, Glasgow, UK.
Br J Pharmacol. 2013 Jul;169(5):1130-9. doi: 10.1111/bph.12209.
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.
二十碳五烯酸（EPA）已被证明在体外可抑制免疫细胞反应，如细胞因子生成及下游前列腺素生成。然而，体内研究将EPA作为鱼油的次要成分使用，结果各异。由于尚未对纯EPA在体内免疫/炎症反应方面进行评估，我们研究了EPA对全身炎症反应的影响。
给兔子静脉注射聚肌苷酸：聚胞苷酸（poly I:C），在口服EPA治疗42天（每日给药）前后进行。还研究了对白细胞介素-1β（IL-1β）和肿瘤坏死因子-α（TNF-α）的反应。在注射poly I:C后立即持续监测体温并采集血样。通过酶免疫测定法测量血浆中IL-1β、前列腺素E2（PGE2）和15-脱氧-Δ（12,14）-前列腺素J2（15d-PGJ2）的水平。
EPA治疗后，与治疗前相比，对poly I:C的发热反应明显受到抑制。这伴随着poly I:C刺激引起的血浆中IL-1β和PGE2水平升高的平行降低。矛盾的是，EPA治疗后15d-PGJ2的水平更高。EPA治疗对IL-1β或TNF-α引起的发热反应或PGE2血浆水平没有显著影响。
口服EPA可通过抑制上游细胞因子生成在体内抑制免疫/炎症反应，导致发热反应降低并间接降低循环中PGE2的水平。EPA还增强了具有细胞保护作用的前列腺素15d-PGJ2的生成，表明EPA具有治疗益处。
