This study was designed to investigate the mechanisms by which marine lipids rich in long chain ω-3 fatty acids inhibit autoimmune disease 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. Proteinuria was detected earlier and became progressively severe in CO-fed mice. The average life span was significantly shortened by the CO diet (266.7 days ± 12.5), whereas FO extended the survival significantly (402.1 days ± 26.1; p < 0.001). A cross- sectional study at 6.5 mo of age revealed an increased proliferative response to T cell mitogens including bacterial superantigens and decreased serum anti-dsDNA Ab titers 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 lower IL-4 production similar to that of young (3.5 mo) mice. Flow cytometric analyses of splenocytes revealed lower Ig+, higher lymphocyte endothelial cell adhesion molecule-1, and lower Pgp-1+ cells within CD4+ and CD8+ subsets in FO-fed mice. Also, elevated IL-2 and IL-4 and significantly higher TGF-β1 and lower c-myc and c-ras mRNA expression and higher TGF-β1 and significantly lower c-Myc and c-Ha-Ras proteins were detected in spleens of FO-fed mice. Fatty acid analysis revealed significantly higher linoleic (18:2ω-6) and arachidonic (20:4ω-6) acid levels in splenocytes of the CO- fed group and higher eicosapentanoic (20:5ω-3) and docosahexanoic (22:6ω- 3) acid levels in the FO-fed group, indicating that changes in membrane fatty acid composition may contribute to the altered immune function and gene expression during the development of murine SLE.
|Original language||English (US)|
|Number of pages||9|
|Journal||Journal of Immunology|
|State||Published - Jun 15 1994|
ASJC Scopus subject areas
- Immunology and Allergy