INCREASED TCF-BETA AND DECREASED ONCOGENE EXPRESSION BY OMEGA-3-FATTY-ACIDS IN THE SPLEEN DELAYS ONSET OF AUTOIMMUNE-DISEASE IN B W MICE/

This study was designed to investigate the mechanisms by which marine lipids rich in long chain omega-3 fatty acids inhibit autoimmune disea se and prolong the survival rate in female (NZB/NZW) F1 (B/W) mice, an animal model for human SLE. Nutritionally adequate semipurified diets containing at 10% either corn oil (CO) or fish oil (FO) were fed from 1 mo of age and were monitored for proteinuria and survival. Proteinu ria was detected earlier and became progressively severe in CO-fed mic e. The average life span was significantly shortened by the CO diet (2 66.7 days +/- 12.5), whereas FO extended the survival significantly (4 02.1 days +/- 26.1; p < 0.001). A cross-sectional study at 6.5 mo of a ge revealed an increased proliferative response to T cell mitogens inc luding bacterial superantigens and decreased serum anti-dsDNA Ab titer s in the FO group compared with the CO group. Furthermore, splenocytes from the FO group when stimulated with Con A had higher IL-2 and lowe r IL-4 production similar to that of young (3.5 mo) mice. Flow cytomet ric analyses of splenocytes revealed lower Ig(+), higher lymphocyte en dothelial cell adhesion molecule-1, and lower Pgp-1(+) cells within CD 4(+) and CD8(+) subsets in FO-fed mice. Also, elevated IL-2 and IL-4 a nd significantly higher TGF-beta 1 and lower c-myc and c-ras mRNA expr ession and higher TGF-beta 1 and significantly lower c-Myc and c-Ha-Ra s proteins were detected in spleens of FO-fed mice. Fatty acid analysi s revealed significantly higher linoleic (18:2 omega-6) and arachidoni c (20:4 omega-6) acid levels in splenocytes of the CO-fed group and hi gher eicosapentanoic (20:5 omega-3) and docosahexanoic (22:6 omega-3) acid levels in the FO-fed group, indicating that changes in membrane f atty acid composition may contribute to the altered immune function an d gene expression during the development of murine SLE.