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

• Published in: Journal of leukocyte biology Vol. 84; no. 4; pp. 900 - 914
• Main Authors: Wu, Dayong, Meydani, Simin Nikbin
• Format: Journal Article
• Language: English
• Published: United States Society for Leukocyte Biology 01.10.2008; The Society for Leukocyte Biology
• Subjects: Aged; aging; Aging - immunology; Aging - physiology; Animals; Antigen-Presenting Cells - immunology; cyclooxygenase; Dinoprostone - metabolism; Humans; immune function; Infection - epidemiology; Infection - immunology; Inflammation - immunology; Inflammation - physiopathology; Inflammation - prevention & control; macrophage; Middle Aged; Models, Animal; prostaglandin; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; Vitamin E - therapeutic use
• ISSN: 0741-5400; 1938-3673
• DOI: 10.1189/jlb.0108023

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 (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 PGE2 production in Mφ. 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 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.