Inflammatory biomarker profiles across frailty stages in older adults

Background

Frailty is a multidimensional syndrome associated with increased vulnerability to adverse health outcomes and has been linked to systemic and neuroinflammatory processes. Blood-based inflammatory biomarkers may help characterise biological differences across frailty stages.

Objectives

To evaluate the association between circulating inflammatory biomarkers and increasing frailty severity in older adults.

Methods

Study in 619 older adults recruited across ambulatory, hospitalised and institutionalised settings. Participants were classified as non-frail, mildly, moderately or severely frail. Plasma IL-1β, IL-6, IL-8, IL-10 and TNF-α were measured using high-sensitivity immunoassays. Given the non-normal distribution of biomarker concentrations, non-parametric analyses were performed.

Results

Valid biomarker data were available for 495–521 participants depending on the analyte. Significant differences across frailty stages were observed for all biomarkers: IL-1β, IL-6, IL-8, IL-10 and TNF-α (all p < 0.001). IL-6 showed the strongest association with frailty severity (H = 183.242), followed by TNF-α (H = 85.439) and IL-10 (H = 61.643), with higher rank distributions in frail groups compared with non-frail participants. IL-1β showed significant but more modest differences (H = 27.573). IL-8 also differed significantly across frailty stages (H = 31.108), but displayed an inverse pattern, with higher ranks in non-frail individuals. In the available post-hoc comparison between mild and advanced frailty, no biomarker remained significant after Bonferroni correction.

Conclusions

Inflammatory biomarkers differ significantly across frailty stages, supporting the existence of distinct inflammatory profiles in older adults. IL-6 and TNF-α emerge as the most strongly associated markers, suggesting that systemic inflammation may contribute to increasing frailty and multidimensional vulnerability. These biomarkers can be an indicator for the early identification of frailty.

Key messages

• Circulating inflammatory biomarkers differ significantly across frailty stages in older adults, supporting the presence of distinct biological inflammatory profiles associated with frailty severity.

• IL-6 and TNF-α showed the strongest association with increasing frailty, suggesting their potential value as early indicators of frailty and multidimensional vulnerability.