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Docosahexaenoic acid reduces inflammation and joint destruction in mice with collagen-induced arthritis

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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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Correspondence to Julie M. Nauroth.

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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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