Wu Dayong, Meydani Simin Nikbin
Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA 02111, USA.
J Leukoc Biol. 2008 Oct;84(4):900-14. doi: 10.1189/jlb.0108023. Epub 2008 Jul 2.
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 (Mphi) 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 Mphi. 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 Mphi 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-kappaB. Similar to Mphi, 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 and the effect of vitamin E as nutritional intervention with a focus on the work conducted in our laboratory.
衰老与免疫和炎症反应失调有关。T细胞功能衰退是免疫衰老最显著且特征最明确的特征。T细胞内部的固有变化和外部因素共同导致了与年龄相关的T细胞功能衰退。衰老过程中出现的T细胞缺陷涉及从早期受体激活事件到克隆扩增的多个阶段。在外部因素中，巨噬细胞（Mphi）产生的T细胞抑制因子前列腺素E2（PGE2）增加最为明显。维生素E可逆转与年龄相关的T细胞缺陷，尤其是初始T细胞。维生素E的这种作用还体现在老年人上呼吸道感染率降低以及啮齿动物模型中流感感染清除率提高。维生素E对T细胞的增强作用是通过其对T细胞的直接作用以及间接抑制Mphi中PGE2的产生来实现的。随着衰老导致的炎症上调因其在疾病发病机制中的影响而受到越来越多的关注。老年Mphi中PGE2产生增加是环氧化酶2（COX-2）表达增加的结果，导致COX酶活性更高，而这又与神经酰胺诱导的核因子κB（NF-κB）上调有关。与Mphi类似，老年小鼠的脂肪细胞中COX-2以及炎症细胞因子白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）的表达也更高，这可能也与神经酰胺水平升高和NF-κB激活有关。本综述将讨论上述与年龄相关的免疫和炎症变化以及维生素E作为营养干预的作用，重点关注我们实验室开展的工作。
