Effects of dietary omega 3 and omega 6 lipids and vitamin E on proliferative response, lymphoid cell subsets, production of cytokines by spleen cells, and splenic protein levels for cytokines and oncogenes in MRL/MpJ-lpr/lprmice

omega 3 Fatty acid rich fish oil (FO) and vitamin E may delay rite progress of certain autoimmune diseases, The present study examined the mechanisms of action of omega 3 lipids and vitamin E in autoimmune-prone MRL/lpr mice suffering from extensive lymphoproliferation, lupus-like symptoms, and acce lerated aging. To determine whether the effects of omega 3 lipids in autoim mune disease is linked to vitamin E levels, weanling female MRL/lpr and con genic control MRL/++ mice were fed diets containing 10% corn oil(CO) or 10% FO at two levels of vitamin E (75 IU or 500 IU/kg diet) for 4 months. The appearance of lymph nodes was delayed in the mice fed FO, and higher levels of FO offered further protection against the appearance of lymph nodes. An alysis of the spleen cells revealed that the cells positive for Thy. I and Fas were significantly higher in the MRL/++ mice. The groups fed high level s of vitamin E generally exhibited higher levels of Fas. The proliferative response of splenocytes of MRL/++ mice to mitogens was significantly higher compared with MRL/lpr mice, Interleukin (IL)-10 production by spleen cells was significantly higher in FO-fed MRL/lpr mice than in CO-fed mice. In mi ce fed a high level of vitamin E, the production of IL-12 and tumor necrosi s factor-alpha was significantly lower and IL-2 was significantly higher th an in animals fed a lower level of vitamin E, Proinflammatory cytokines wer e higher in the MRL/lpr mice and both FO and vitamin E lowered the levels o f proinflammatory cytokines and lipid mediators. Western blots revealed tha t c-myc and c-ras were significantly lower and IL-2 and transforming growth factor. (TGF)-beta 1 levels were significantly higher in the spleens of MR L/++ mice. FO lowered c-myc and high levels of vitamin E in the diets norma lized the levels of TGF-beta 1 in MRL/lpr mice. The observations from this study suggest that both FO and vitamin E modulate the levels of specific cy tokines, decrease the Icl cls of proinflammatory cytokines, inflammatory li pid mediators, and c-myc, and increase TGF-beta 1 levels in spleens of MRL/ lpr,nice and thus may delay the progress autoimmune diseases. (C) Elsevier Science Inc. 1999. All rights reserved.