Division of Geriatric Medicine and Gerontology, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
Aging Dis. 2011 Dec;2(6):466-73. Epub 2011 Dec 2.
Frailty is an important geriatric syndrome that is characterized by multisystem dysregulation, leading to decreased physiological reserve and increased vulnerability for adverse health outcomes. A large number of studies have shown a heightened inflammatory state marked by elevated levels of inflammatory molecules, such as IL-6 and C-reactive protein (CRP), and increased counts of white blood cell (WBC) and WBC subpopulations in frail older adults. It has been postulated that this heightened inflammatory state, or chronic inflammation, may play an important role in the pathogenesis of frailty, directly or through its detrimental influence to other physiologic systems. Inflammatory and immune activation mediated by monocytes and macrophages demonstrated by upregulated expression of specific stress responsive inflammatory pathway genes and elevated neopterin levels may contribute, at least in part, to this chronically heightened inflammatory state in frailty. Decrease in lipopolysaccharide (LPS)-induced proliferation of the peripheral blood mononuclear cells (PBMCs), one of the functional readouts of the innate immune system, has also been observed in frail older adults. In the adaptive immune system, significant frailty-associated alterations have been identified in the T-cell compartment including expansion of CD8(+) and CCR5(+) T cells and loss of CD28 expression, above and beyond age-related senescent remodeling. Moreover, frailty is associated with impaired antibody responses to pneumococcal and influenza immunization and poor clinical protection against influenza infection in community-dwelling older adults. Taken together, these findings demonstrate significant inflammatory and immune dysregulation in frail older adults and highlight the need for strategies to improve the immune function for this vulnerable elderly population.
衰弱是一种重要的老年综合征，其特征是多系统失调，导致生理储备减少和对不良健康结果的易感性增加。大量研究表明，衰弱的老年人存在明显的炎症状态，表现为炎症分子（如 IL-6 和 C 反应蛋白（CRP））水平升高，白细胞（WBC）和 WBC 亚群计数增加。有人推测，这种增强的炎症状态或慢性炎症可能在衰弱的发病机制中发挥重要作用，直接或通过其对其他生理系统的有害影响。单核细胞和巨噬细胞介导的炎症和免疫激活，通过上调特定应激反应性炎症途径基因的表达和升高的新蝶呤水平来证明，至少部分地导致了衰弱的这种慢性炎症状态。外周血单个核细胞（PBMCs）中脂多糖（LPS）诱导的增殖减少也在衰弱的老年人中观察到，这是固有免疫系统的一种功能读数。在适应性免疫系统中，在 T 细胞区室中已经确定了与衰弱相关的显著改变，包括 CD8（+）和 CCR5（+）T 细胞的扩增以及 CD28 表达的丧失，超出了与年龄相关的衰老重塑。此外，衰弱与肺炎球菌和流感免疫接种的抗体反应受损以及社区居住的老年人中流感感染的临床保护不良有关。总之，这些发现表明衰弱的老年人存在明显的炎症和免疫失调，并强调需要制定策略来改善这一脆弱老年人群的免疫功能。
