ARS | Publication request: Age-associated changes in immune and inflammatory response: role of nutritional intervention

Submitted to: Journal of Leukocyte Biology
Publication Type: Review Article
Publication Acceptance Date: June 13, 2008
Publication Date: October 1, 2008
Citation: Wu, D., Meydani, S. 2008. Age-associated changes in immune and inflammatory response: role of nutritional intervention. Journal of Leukocyte Biology. 84:900-914.

Technical Abstract: Aging is associated with dysregulated immune and inflammatory responses. Declined T cell function is best characterized in immuno-senescence. Both intrinsic changes within T cells and extrinsic factors contribute to the age-associated decline in T cell function. T cell defect involves multiple stages from early receptor activation events to ultimate clonal expansion, many of which are adversely affected by aging. Among extrinsic factors, increased production of T cell suppressive factor PGE2 by macrophages is most recognized. Vitamin E reverses age-associated defect in T cells, particularly naïve T cells. This effect of vitamin E is also reflected in reduced rate of upper respiratory tract infection in the elderly and enhanced clearance of influenza infection in rodent model. T cell-enhancing effect of vitamin E is accomplished via its direct effect on T cells and indirectly by inhibiting PGE2 production in macrophages. Upregulated inflammation with aging has attracted increasing attention due to its implications in pathogenesis of diseases. Increased PGE2 production in old macrophages'is due to increased COX-2 expression leading to higher COX enzyme activity, in which the ceramide-induced up-regulation of NF-kappaB activation may be a central mechanism. Our recent studies showed that similar to macrophages, 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 with a focus on the work conducted in our laboratory.