Age-associated changes in immune and inflammatory responses: impact of vitamin E intervention

Dayong Wu^* and Simin Nikbin Meydani^*^,^,1

^* Nutritional Immunology Laboratory, Jean Mayer USDA, Human Nutrition Research Center on Aging at Tufts University, and
Department of Pathology, Sackler Graduate School of Biochemical Sciences, Tufts University, Boston, Massachusetts, USA

¹ Correspondence: Nutritional Immunology Laboratory, Jean Mayer USDA-HNRCA at Tufts University, Friedman School of Nutrition Science and Policy, and Sackler Graduate School at Tufts University, 711 Washington St., Boston, MA 02111, USA. E-mail: simin.meydani{at}tufts.edu

ABSTRACT

Aging is associated with dysregulated immune and inflammatoryresponses. Declining T cell function is the most significantand best-characterized feature of immunosenescence. Intrinsicchanges within T cells and extrinsic factors contribute to theage-associated decline in T cell function. T cell defect seenin aging involves multiple stages from early receptor activationevents to clonal expansion. Among extrinsic factors, increasedproduction of T cell-suppressive factor PGE₂ by macrophages(M ${phi}$ ) is most recognized. Vitamin E reverses an age-associateddefect in T cells, particularly naïve T cells. This effectof vitamin E is also reflected in a reduced rate of upper respiratorytract infection in the elderly and enhanced clearance of influenzainfection in a rodent model. The T cell-enhancing effect ofvitamin E is accomplished via its direct effect on T cells andindirectly by inhibiting PGE₂ production in M ${phi}$ . Up-regulatedinflammation with aging has attracted increasing attention asa result of its implications in the pathogenesis of diseases.Increased PGE₂ production in old M ${phi}$ is a result of increasedcyclooxygenase 2 (COX-2) expression, leading to higher COX enzymeactivity, which in turn, is associated with the ceramide-inducedup-regulation of NF- ${kappa}$ B. Similar to M ${phi}$ , adipocytes from old micehave a higher expression of COX-2 as well as inflammatory cytokinesIL-1β, IL-6, and TNF- ${alpha}$ , which might also be related to elevatedlevels of ceramide and NF- ${kappa}$ B activation. This review will discussthe above age-related immune and inflammatory changes and theeffect of vitamin E as nutritional intervention with a focuson the work conducted in our laboratory.

Key Words: aging • immune function • macrophage • prostaglandin • cyclooxygenase