Immunomodulation with eicosapentaenoic acid supports the treatment of autoimmune small-vessel vasculitis.
Immunomodulation with eicosapentaenoic acid supports the treatment of autoimmune small-vessel vasculitis.
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DOI：
10.1038/srep06406
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发表时间：
2014-09-18
影响因子：
4.6
通讯作者：
Fujita T
中科院分区：
文献类型：
--
作者：
Hirahashi J;Kawahata K;Arita M;Iwamoto R;Hishikawa K;Honda M;Hamasaki Y;Tanaka M;Okubo K;Kurosawa M;Takase O;Nakakuki M;Saiga K;Suzuki K;Kawachi S;Tojo A;Seki G;Marumo T;Hayashi M;Fujita T
小血管炎是一种危及生命的自身免疫性疾病，通常与抗中性粒细胞胞浆抗体（ANCA）有关。包括类固醇和环磷酰胺在内的常规免疫疗法可引起严重的不良事件，限制治疗的有效性和安全性。二十碳五烯酸（EPA）是鱼油的关键成分，是一种欧米茄-3多不饱和脂肪酸，众所周知具有心脏保护作用，有益于血管功能。我们报告了两例全身性ANCA相关性血管炎（AAV）的老年患者，在不使用额外的免疫抑制剂的情况下，EPA联合类固醇安全地诱导并维持了缓解。为了探索EPA增强AAV治疗的机制，我们采用SCG/Kj小鼠作为AAV的自发鼠模型。富含EPA的膳食显著延迟了新月体肾小球肾炎的发病，并延长了总生存期。EPA衍生的抗炎脂质介质及其前体存在于EPA处理的小鼠的肾脏、血浆、脾脏和肺中。此外，在EPA处理的小鼠中观察到肾脏淋巴结中ANCA产生和CD 4/CD 8双阴性T细胞的减少以及Foxp 3+调节性T细胞的增加。这些临床和实验观察结果表明，EPA可以安全地支持和增强治疗自身免疫性小血管炎的常规治疗。
Small-vessel vasculitis is a life-threatening autoimmune disease that is frequently associated with anti-neutrophil cytoplasmic antibodies (ANCAs). Conventional immunotherapy including steroids and cyclophosphamide can cause serious adverse events, limiting the efficacy and safety of treatment. Eicosapentaenoic acid (EPA), a key component of fish oil, is an omega-3 polyunsaturated fatty acid widely known to be cardioprotective and beneficial for vascular function. We report two elderly patients with systemic ANCA-associated vasculitis (AAV) in whom the administration of EPA in concert with steroids safely induced and maintained remission, without the use of additioal immunosuppressants. To explore the mechanisms by which EPA enhances the treatment of AAV, we employed SCG/Kj mice as a spontaneous murine model of AAV. Dietary enrichment with EPA significantly delayed the onset of crescentic glomerulonephritis and prolonged the overall survival. EPA-derived anti-inflammatory lipid mediators and their precursors were present in the kidney, plasma, spleen, and lungs in the EPA-treated mice. Furthermore, a decrease in ANCA production and CD4/CD8-double negative T cells, and an increase in Foxp3+ regulatory T cells in the lymph nodes of the kidney were observed in the EPA-treated mice. These clinical and experimental observations suggest that EPA can safely support and augment conventional therapy for treating autoimmune small-vessel vasculitis.
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