Benjumin Hsu1,2,3, Vasant Hirani2,3,4, Robert G Cumming1,2,3,5, Vasi Naganathan2, Fiona M Blyth2, Fredrick C Wright2, Louise M Waite2, Markus J Seibel1, David J Handelsman1, David G Le Couteur1,2,4. 1. ANZAC Research Institute, University of Sydney and Concord Hospital, New South Wales, Australia. 2. Centre of Education and Research on Ageing, University of Sydney and Concord Hospital, New South Wales, Australia. 3. ARC Centre of Excellence in Population Ageing Research, University of Sydney, New South Wales, Australia. 4. Charles Perkins Centre, University of Sydney, New South Wales, Australia. 5. School of Public Health, University of Sydney, New South Wales, Australia.
Abstract
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.
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.
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