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Effects of Dietary -3 and -6 Lipids and Vitamin E on Serum Cytokines, Lipid Mediators and Anti-DNA Antibodies in a Mouse Model for Rheumatoid Arthritis

Department of Physical Therapy, Exercise and Nutrition Sciences, State University of New York at Buffalo, 15 Farber Hall, Buffalo, New York

Objective: Omega-3 (-3) fatty acid rich-fish oil (FO) and vitamin E (vit-E) may delay the progress of certain autoimmune diseases. The present study examined the mechanism of action of -3 and -6 lipids and vit-E on the serum cytokines and lipid mediators in autoimmune-prone MRL/lpr mice (a model for rheumatoid arthritis, RA). The lpr (lymphoproliferative) gene is overexpressed in these mice causing extensive lymphoproliferation, lupus-like symptoms and accelerated aging.

Methods: Weanling female MRL/lpr and congenic control MRL/++ mice were fed 10% corn oil (CO, 6) or FO-based semipurified diets containing two levels of vitamin E (vit-E-75, I.U. and vit-E-500 I.U./Kg diet) for four months. At the end of the experiment, serum anti-DNA antibodies, cytokines and lipid mediators levels were determined.

Results: The appearance of enlarged lymph nodes was delayed in the mice fed FO, and the FO-500 IU vit-E diet offered further protection against enlargement of lymph nodes. The MRL/lpr mice exhibited significantly higher levels of serum anti-dsDNA antibodies. The FO-fed mice had significantly lower serum IL-6, IL-10, IL-12, TNF-, PGE₂, TXB₂ and LTB₄ levels compared with CO-fed mice. In mice fed 500 IU vit-E diets, the serum IL-6, IL-10, IL-12 and TNF- levels were significantly lower and serum IL-1ß was significantly higher compared to 75 IU-vit-E-fed mice in CO/FO or both. The levels of anti-DNA antibodies, IL-4, IL-6, TNF-, IL-10 and IL-12 were higher in the sera of MRL/lpr mice. The FO diet lowered the levels of these cytokines (except IL-4) and lipid mediators. Adding 500 IU of vit-E to the FO diet further lowered the levels of IL-6, IL-10, IL-12, and TNF-.

Conclusion: It is clear from our observations that the beneficial effects of FO can be enhanced by the addition of 500 IU of vit-E in the diet. The FO diet containing 500 IU of vit-E may specifically modulate the levels of IL-6, IL-10, IL-12 and TNF- and thereby may delay the onset of autoimmunity in the MRL/lpr mouse model. The observations from this study may form a basis for selective nutrition intervention based on specific fatty acids and antioxidants in delaying the progress of RA.

Key words: -3 lipids, fish oil, vit-E, cytokines, lipid mediators

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