We have previously shown that dietary fish oil (FO), relative to corn oil (CO), and/or calorie restriction (CR) increases the lifespan of NZBxNZW by delaying the onset of autoimmune renal disease. To better understand the mechanism of action we determined the effects of dietary FO (10% v/w) and/or CR (40%) with respect to age on peripheral blood T-lymphocyte cytokine production. Blood cells were activated with PMA and ionomycin for four hours in the presence of brefeldin A, stained for the CD4 and CD8 T-lymphocyte subsets and intracellular cytokine accumulation of interleukins-2 (IL-2), -5 (IL-5), -10 (IL-10), and IFN-gamma (IFN-γ) and analyzed by flow cytometry. Our results show that the relative percent of CD4 and CD8 T-lymphocytes decrease by 50% in old (9 mo) versus young (4 mo) mice. In general, aging caused a rise in the percent of CD4 T-lymphocytes producing IL-2 (4-fold), IFN-γ (6-fold), and IL-5 (3-fold) but did not effect IL-10 production. Similar, but less dramatic results were obtained in CD8 T-lymphocytes. While dietary FO or CR partially normalized CD4 cells in aged mice, the combination of FO/CR completely normalized CD4 cells. In CD8 T-lymphocytes, CR alone normalized the age-dependent decrease. CR completely blunted the rise in the percent of IL-2 and IFN-γ producing CD4 and CD8 T-lymphocytes while FO had only a partial effect. Surprisingly, FO abolished IL-5 and IL-10 production in young and old CD8 T-lymphocytes. In contrast, FO and CR were equally effective in suppressing IL-5 production in aged CD4 T-lymphocytes. We show, for the first time, that dietary FO and CR dramatically down-regulate key immunoregulatory cytokines involved in autoimmune disease.
|Original language||English (US)|
|State||Published - Mar 20 1998|
ASJC Scopus subject areas
- Molecular Biology