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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0108023

Received for publication January 12, 2008.
Revised May 30, 2008.
Accepted for publication June 15, 2008.

Article

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

Dayong Wu * and Simin Nikbin Meydani *{dagger}@

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

@ To whom correspondence should be addressed. E-mail: simin.meydani{at}tufts.edu.


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Abstract

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 PGE2 by macrophages (M{phi}) 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 PGE2 production in M{phi}. Up-regulated inflammation with aging has attracted increasing attention as a result of its implications in the pathogenesis of diseases. Increased PGE2 production in old M{phi} 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-{kappa}B. Similar to M{phi}, adipocytes from old mice have a higher expression of COX-2 as well as inflammatory cytokines IL-1{beta}, IL-6, and TNF-{alpha}, which might also be related to elevated levels of ceramide and NF-{kappa}B 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.

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




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