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Age‐associated changes in immune and inflammatory responses: impact of vitamin E intervention
Author(s) -
Wu Dayong,
Meydani Simin Nikbin
Publication year - 2008
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0108023
Subject(s) - immunosenescence , immune system , biology , inflammation , immunology , t cell , cytokine , tumor necrosis factor alpha , ceramide , endocrinology , medicine , cancer research , apoptosis , biochemistry
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 (Mφ) 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 Mφ. 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 Mφ 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‐κB. Similar to Mφ, adipocytes from old mice have a higher expression of COX‐2 as well as inflammatory cytokines IL‐1β, IL‐6, and TNF‐α, which might also be related to elevated levels of ceramide and NF‐κB 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.