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

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.

• Authors: Junichi Hirahashi, Kimito Kawahata, Makoto Arita, Ryo Iwamoto, Keiichi Hishikawa, Mie Honda, Yoshifumi Hamasaki, Mototsugu Tanaka, Koshu Okubo, Miho Kurosawa, Osamu Takase, Masanori Nakakuki, Kan Saiga, Kazuo Suzuki, Shoji Kawachi, Akihiro Tojo, George Seki, Takeshi Marumo, Matsuhiko Hayashi, Toshiro Fujita
• Journal: Scientific reports (Sci Rep) Vol. 4 Pg. 6406 (Sep 18 2014) ISSN: 2045-2322 [Electronic] England
• PMID: 25230773 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• RNA, Messenger
• Eicosapentaenoic Acid

Topics

• Aged
• Animals
• Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis (drug therapy, immunology, pathology)
• Blotting, Western
• CD4-Positive T-Lymphocytes
• CD8-Positive T-Lymphocytes
• Cell Proliferation
• Cells, Cultured
• Disease Models, Animal
• Eicosapentaenoic Acid (therapeutic use)
• Female
• Humans
• Immunoenzyme Techniques
• Immunomodulation (drug effects)
• Male
• Mice
• Mice, Inbred Strains
• RNA, Messenger (genetics)
• Real-Time Polymerase Chain Reaction
• Reverse Transcriptase Polymerase Chain Reaction