Effects of dietary omega-3 and omega-6 lipids and vitamin E on serum cytokines, lipid mediators and anti-DNA antibodies in a mouse model for rheumatoid arthritis

Objective: Omega-3 (omega-3) fatty acid rich-fish oil (FO) and vitamin E (v it-E) may delay the progress of certain autoimmune diseases. The present st udy examined the mechanism of action of omega-3 and omega-6 lipids and vit- E on the serum cytokines and lipid mediators in autoimmune-prone MRL/1pr mi ce (a model for rheumatoid arthritis, RA). The 1pr (lymphoproliferative) ge ne is overexpressed in these mice causing extensive lymphoproliferation, lu pus-like symptoms and accelerated aging. Methods: Weanling female MRL/lpr and congenic control MRL/+ + mice were fed 10% corn oil (CO, omega 6) or FO-based semipurified diets containing two l evels of vitamin E (vit-E-75, I.U. and vit-E-500 I.U/Kg diet) for four mont hs. 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 enlarg ement of lymph nodes. The MRL/lpr mice exhibited significantly higher level s of serum anti-dsDNA antibodies. The FO-fed mice had significantly lower s erum IL-6, IL-IO, IL-12, TNF-alpha PGE(2), TXB2 and LTB4 levels compared wi th GO-fed mice. In mice fed 500 TU vit-E diets, the serum IL-6, lL-10, IL-1 2 and TNF-alpha levels were significantly lower and serum IL-1 beta was sig nificantly higher compared to 75 IU-vit-E-fed mice in CO/FO or both. The le vels of anti-DNA antibodies, IL-4, IL-6, TNF-alpha, IL-10 and IL-12 were hi gher in the sera of MRL/lpr mice. The FO diet lowered the levels of these c ytokines (except IL-4) and lipid mediators. Adding 500 IU of vit-E to the F O diet further lowered the levels of IL-6, IL-10, IL-22, and TNF-alpha. Conclusion: ft is clear from our observations that the beneficial effects o f 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-alpha and thereby may delay the onset of autoimmuni ty in the MRL/lpr mouse model. The observations from this study may form a basis for selective nutrition intervention based on specific fatty acids an d antioxidants in delaying the progress of RA.