Abstract
Objective
This study was designed to determine the anti-inflammatory 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-1β, interferonγ 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.
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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-1β:
-
Interleukin-1 beta
- IL-10:
-
Interlukin-10
- IFNγ:
-
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
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Acknowledgments
The authors would like to thank Alison Bendele [Bolder BioPATH, Inc.] and Mike Bendele [Bolder BioPATH, Inc.] for assistance in running the arthritis model. Eileen Bailey-Hall [DSM] and Gloria Chung [DSM] are acknowledged for their technical assistance and Irina Dahms [DSM] for diet formulation advice.
This research was solely funded by DSM Nutritional Products where all the authors are currently or were formerly employed. Authors may hold patents.
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Olson, M.V., Liu, YC., Dangi, B. et al. Docosahexaenoic acid reduces inflammation and joint destruction in mice with collagen-induced arthritis. Inflamm. Res. 62, 1003–1013 (2013). https://doi.org/10.1007/s00011-013-0658-4
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DOI: https://doi.org/10.1007/s00011-013-0658-4