Docosahexaenoic acid reduces inflammation and joint destruction in mice with collagen-induced arthritis
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Inflammation Research
ORIGINAL RESEARCH PAPER
Docosahexaenoic acid reduces inflammation and joint destruction in mice with collagen-induced arthritis Melissa V. Olson • Ying-Chun Liu • Bindi Dangi • J. Paul Zimmer Norman Salem Jr. • Julie M. Nauroth
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Received: 20 December 2012 / Accepted: 14 August 2013 / Published online: 6 September 2013 Ó Springer Basel 2013
Abstract Objective This study was designed to determine the antiinflammatory activity of docosahexaenoic acid (DHA), alone and in combination with eicosapentaenoic acid (EPA), in a murine model of rheumatoid arthritis, collagen induced arthritis (CIA). Methods The CIA was induced in DBA/1OlaHsd mice by the injection of bovine type II collagen in Freunds’s complete adjuvant on days 0 and 21. Mice were fed modified diets containing DHA and/or EPA for 4 weeks prior to the initial collagen injection until study termination at day 45. The severity of CIA was assessed by measuring erythema, edema and mobility of the digits on the fore and hind paws, as well as histology. The level of serum anti-collagen antibodies was determined by ELISA. The ex vivo effects of DHA and/or EPA on splenocyte proliferation and cytokine production were evaluated by BrdU method and ELISA. Results Prophylactic treatment with DHA, and not DHA/ EPA, significantly reduced arthritis severity and joint damage. Treatment with DHA also decreased anti-collagen (CII) antibodies in vivo, downregulated interleukin-1b, interferonc and upregulated protective interleukin-10 ex vivo. Conclusion Prophylactic treatment with DHA was efficacious in a mouse model of rheumatoid arthritis and may be a useful intervention strategy against inflammatory arthritis. Keywords Docosahexaenoic acid Polyunsaturated fatty acids Inflammation Arthritis Responsible Editor: John Di Battista. M. V. Olson Y.-C. Liu B. Dangi J. Paul Zimmer N. Salem Jr. J. M. Nauroth (&) DSM Nutritional Products, 6480 Dobbin Road, Columbia, MD 21045, USA e-mail: [email protected]
Abbreviations AIN American Institute of Nutrition AA Arachidonic acid AUC Area under the curve CII Collagen II CIA Collagen induced arthritis COX Cycloxygenase DHA Docosahexaenoic acid EPA Eicosapentaenoic acid EE Ethyl esters FLAX Flax seed oil HO-SAFF High-oleic safflower oil HCOC Hydrogenated coconut oil IgG Immunoglobulin IL-1b Interleukin-1 beta IL-10 Interlukin-10 IFNc Interferon gamma LPS Lipopolysaccharide LC-n3 Long chain omega-3 OA Oleic acid PUFA Polyunsaturated fatty acids RA Rheumatoid arthritis SOY Soybean oil TG Triglyceride
Introduction Numerous studies have demonstrated that long-chain omega-3 (LC-n3) polyunsaturated fatty acids (PUFA) have anti-inflammatory properties, suggesting that they may be beneficial as therapies in inflammation-driven disorders such as cardiovascular disease [1], arthritis [2], and inflammatory bowel disease [3]. LC-n3 PUFA, such as
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docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are important constituents of the phospholipids of all cell membranes, where they play a role in
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