DIETARY MODULATION OF THE IMMUNE-RESPONSE IN THE AGED

The age-associated changes of the immune response are well documented. However, the biochemical changes leading to these alterations are not well-defined. A series of experiments using dietary antioxidants and prooxidants were conducted in old mice and older adults to determine the contribution of lipid peroxides, especially that of oxidative products of arachidonic acid in the age-associated decline of the immune response. Splenocytes from old mice and peripheral blood mononuclear cells (PBMC) from older adults produced significantly more PGE2 and their plasma had higher TBAR levels than their young counter-parts. Vitamin E supplementation of both old mice and older adults decreased PGE2 synthesis while increasing IL-2 production, mitogenic response to Con A and the delayed hypersensitivity skin test (DTH). Older adults supplemented with vitamin E showed a significant reduction in plasma TBAR. Supplementation with another dietary antioxidant, glutathione (GSH) (0.1 to 1% by wt of diet for 4 wk), significantly improved a mitogenic response to Con A and PHA and DTH to DNFB in 17 and 24 mo old mice. This effect was due to an increase in spleen GSH level and not to a change in PGE2 synthesis. On the other hand, supplementation of older women with fish oil containing highly unsaturated n-3 fatty acids, EPA and DHA (2.4 g/day for 3 mo) decreased cytokine production (IL-1, IL-2, IL-6, TNF), mitogenic response of PBMC to PHA and their production of PGE2. Thus, supplementation with dietary antioxidants increases and with dietary prooxidants decreases immune responsiveness of aged. These effects are mediated via changes in the formation of PGE2 and other lipid peroxides.