Aging is associated with a decline in immunological vigor which can contribute to development of age-associated diseases. Nutritional manipulation of the aged immune system presents a practical approach to improving immune response. However, in depth studies of nutrition and the immune system especially as they relate to aging, are lacking. We have shown that macrophages (Mo) from aged mice and humans synthesize more PGE2 (shown to have suppressing effect on cell-mediated immunity) than young mice and humans. Furthermore, vitamin E supplementation decreases PGE2 production and enhances IL-2 production an lymphocyte mitogenesis in aged mice and humans. It is proposed that increases in Mo-mediated suppression via cyclooxygenase and lipoxygenase metabolites of arachidonic acid (AA), i.e., PGE2, leukotriene (LT), hydroxyeicosatetranoic acid (HETE) of H2O2 formation, contributes to the age-associated decrease in IL-2 production and lymphocyte proliferation. Furthermore, vitamin E supplementation, through antioxidant dampening of cyclooxygenase or lipoxygenase or terminating propagation of lipid peroxidation will decrease this suppression, thereby increasing IL-2 production and lymphocyte mitogenesis. To test this hypothesis we will: 1) compare Mo production of AA metabolites, H2O2 and IL-2 and IL-1 production by mixtures of splenic Mo and T cells from young and old mice fed semi-purified diets with 30 or 500 ppm vitamin E. The contribution of each metabolite will be further assessed by addition of its inhibitor or the metabolite itself to these cultures. The effect of in vitro addition of vitamin E will be compared to that of cyclooxygenase and lipoxygenase inhibitors, catalase and supplementation of vitamin E with different levels of tocopherol (30, 60, 120, 240, 500 ppm) on the immune response of mice will be studied. Through these studies: 1) the contribution of oxidative Mo metabolites to age- associated changes in immune function will be studied; 2) the mechanism of the immunostimulatory effect of vitamin E in mice will be delineated; and 3) an appropriate dietary level of tocopherol for optimal immune responsiveness in aged mice and the continuation of the effect over long periods of time will be determined.
Showing the most recent 10 out of 27 publications