title: Frailty, inflammation, and immunity.
abstract: 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.
authors.affiliation: Division of Geriatric Medicine and Gerontology, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
authors.forename: Huifen
authors.initials: H
authors.lastname: Li
authors.forename: Bhavish
authors.initials: B
authors.lastname: Manwani
authors.forename: Sean X
authors.initials: SX
authors.lastname: Leng