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Sci Rep. 2014 Sep 18;4:6406. doi: 10.1038/srep06406.

Immunomodulation with eicosapentaenoic acid supports the treatment of autoimmune small-vessel vasculitis.

Author information

1
1] Department of Nephrology and Endocrinology, Graduate School of Medicine, The University of Tokyo [2] Apheresis and Dialysis Center, School of Medicine, Keio University.
2
Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo.
3
1] Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo [2].
4
Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo.
5
Department of Advanced Nephrology and Regenerative Medicine, Graduate School of Medicine, The University of Tokyo.
6
Department of Nephrology and Endocrinology, Graduate School of Medicine, The University of Tokyo.
7
Development Research, Pharmaceutical Research Center, Mochida Pharmaceutical Co., Ltd.
8
Pharmaceutical Research Laboratories, Nippon Kayaku Co. Ltd.
9
Inflammation Program, Chiba University Graduate School of Medicine.
10
Division of Anesthesia, Surgical Operation Department, National Center for Global Health and Medicine.
11
Clinical Epigenetics, Research Center for Advanced Science and Technology, The University of Tokyo.
12
Apheresis and Dialysis Center, School of Medicine, Keio University.
13
1] Department of Nephrology and Endocrinology, Graduate School of Medicine, The University of Tokyo [2] Clinical Epigenetics, Research Center for Advanced Science and Technology, The University of Tokyo.

Abstract

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.

PMID:
25230773
PMCID:
PMC4166948
DOI:
10.1038/srep06406
[Indexed for MEDLINE]
Free PMC Article

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