Innate Immunity and Frailty

A small number of studies have demonstrated a dysregulation of the innate immune system in frailty. Frail adults have raised white cell and neutrophil count. This remains significantly elevated even after adjustment for common confounders [6668]. Raised neutrophils are also associated with low levels of physical activity and frailty [69]. High white cell count can predict frailty at a ten year follow up [70]. An association has been demonstrated between frailty and the upregulation of monocytic expression of CXCL 10 gene which codes for a potent pro-inflammatory che- mokine [71].

Adaptive Immunity and Frailty

A small number of studies have described the dysregulation of the adaptive immune system in frailty, but the results have been conflicting

A prospective review of response to vaccination showed a reduction in adaptive immune function in frail individuals [72]. However, the study did not attempt to investigate the individual roles of T and B cells in poor response to vaccination. Initial work into frailty in HIV patients demonstrated higher levels of frailty in HIV positive patients compared to non-HIV infected age matched controls [73] and subsequently that CD4+ T cell count can predict the development of frailty in HIV positive men independent of HAART and plasma viral load [45]. Research into T cell subset expression in frailty has revealed conflicting results, particularly in the investigation of CD4:CD8 ratio which has both been positively [68, 74] and inversely associated with frailty [75,76]. The association of CMV with frailty is also unclear. Frailty has been associated with higher titres of CMV IgG [77,78] and also higher levels of CD8+CD28- T cells [74, 76]. CD8+CD28- T cells are highly associated with seropositivity to persistent infections such as CMV. However, the extremely high prevalence of CMV in all older adults make these data difficult to interpret. Only one study has investigated the B cells of a frail population and showed that with increasing age the diversity of the B cell population decreases and this correlates with poor health [79].

To date there is limited research describing a direct relationship between frailty, and immunesenescence or inflammageing. However, initial results have demonstrated an association of frailty with a state of chronic inflammation and dysregulation of both the innate and adaptive immune system. It has also established that immunesenes- cence and inflammageing predate a diagnosis of frailty suggesting a causative role.

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