Cross-Sectional and Longitudinal Relationships Between Inflammatory Biomarkers and Frailty in Community-dwelling Older Men: The Concord Health and Ageing in Men Project

Background: Previous studies demonstrated associations between IL-6 and frailty, but associations between a wide range of cytokines, chemokines, and growth factors with prevalent and incident frailty has not been studied.

Methods: Community-dwelling men aged more than 75 enrolled in the 5-year and 8-year follow-up of the CHAMP study were assessed. Twenty-seven inflammatory biomarkers were measured using the Bio-Plex Pro Human Cytokine 27-plex Assay kit at 5-year follow-up. Frailty was determined using the Fried frailty phenotype (FP) and Rockwood frailty index (FI) at both time-points. Age, body mass index, smoking, alcohol, and comorbidity were also assessed.

Results: In cross-sectional analysis of the 5-year follow-up, the unadjusted odds ratio (OR) for frail versus robust evaluated by the FP showed significant associations for IL-6 (OR: 1.56, 95% confidence interval [CI]: 1.23-1.98) and IL-8 (OR: 1.28, 95% CI: 1.00-1.63). IL-6 remained significantly associated in the age-adjusted (OR: 1.58, 95% CI: 1.21-2.05) and multivariable-adjusted model (OR: 1.54, 95% CI: 1.16-2.05). No associations were observed between pre-frail versus robust. In longitudinal unadjusted analysis, IL-8 (OR: 1.32, 95% CI: 1.03-1.70) and IP-10 (OR: 1.32, 95% CI: 1.03-1.70) at 5-year predicted incident frailty at 8-year follow-up. IL-8 remained longitudinally associated with incident frailty after age (OR: 1.34, 95% CI: 1.03-1.75) but not multivariable (OR: 1.20, 95% CI: 0.98-1.70) adjustment. Similar results were seen using the FI. None of the other biomarkers had significant associations with incident frailty.

Conclusions: Our findings suggest that IL-6 and IL-8 may be cross-sectionally associated with frailty and that all measured inflammatory biomarkers were not causally related to frailty. Together with previous studies, the results suggest that frailty is specifically linked to IL-6 and IL-8 rather than simply representing a nonspecific pan-inflammatory condition.