Age-associated changes in immune and inflammatory responses: impact of vitamin E intervention.
Aging is associated with dysregulated immune and inflammatory responses. Declining T cell function is the most significant and best-characterized feature of immunosenescence. Intrinsic changes within T cells and extrinsic factors contribute to the age-associated decline in T cell function. T cell defect seen in aging involves multiple stages from early receptor activation events to clonal expansion. Among extrinsic factors, increased production of T cell-suppressive factor PGE(2) by macrophages (Mphi) is most recognized. Vitamin E reverses an age-associated defect in T cells, particularly naïve T cells. This effect of vitamin E is also reflected in a reduced rate of upper respiratory tract infection in the elderly and enhanced clearance of influenza infection in a rodent model. The T cell-enhancing effect of vitamin E is accomplished via its direct effect on T cells and indirectly by inhibiting PGE(2) production in Mphi. Up-regulated inflammation with aging has attracted increasing attention as a result of its implications in the pathogenesis of diseases. Increased PGE(2) production in old Mphi is a result of increased cyclooxygenase 2 (COX-2) expression, leading to higher COX enzyme activity, which in turn, is associated with the ceramide-induced up-regulation of NF-kappaB. Similar to Mphi, adipocytes from old mice have a higher expression of COX-2 as well as inflammatory cytokines IL-1beta, IL-6, and TNF-alpha, which might also be related to elevated levels of ceramide and NF-kappaB activation. This review will discuss the above age-related immune and inflammatory changes and the effect of vitamin E as nutritional intervention with a focus on the work conducted in our laboratory.
Wu
Dayong
D
Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA 02111, USA.
Meydani
Simin Nikbin
SN
D000368:Aged; D000375:Aging / Q000276:immunology / Q000502:physiology*; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D015232:Dinoprostone / Q000378:metabolism; D006801:Humans; D007239:Infections / Q000453:epidemiology / Q000276:immunology; D007249:Inflammation / Q000276:immunology* / Q000503:physiopathology* / Q000517:prevention & control; D008875:Middle Aged; D023421:Models, Animal; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014810:Vitamin E / Q000627:therapeutic use
D014810:Vitamin E; D015232:Dinoprostone