ANZAC Research Institute, University of Sydney and Concord Hospital, New South Wales, Australia.
Centre of Education and Research on Ageing, University of Sydney and Concord Hospital, New South Wales, Australia.
J Gerontol A Biol Sci Med Sci. 2019 May 16;74(6):835-841. doi: 10.1093/gerona/glx142.
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.
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.
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.
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.
先前的研究表明白细胞介素-6（IL-6）与虚弱之间存在关联，但广泛的细胞因子、趋化因子和生长因子与普遍和新发虚弱之间的关联尚未得到研究。
本研究纳入了年龄大于 75 岁、参加 CHAMP 研究 5 年和 8 年随访的社区居民。在 5 年随访时使用 Bio-Plex Pro 人类细胞因子 27 plex 检测试剂盒测量了 27 种炎症生物标志物。在两个时间点均使用 Fried 虚弱表型（FP）和 Rockwood 虚弱指数（FI）来确定虚弱。还评估了年龄、体重指数、吸烟、饮酒和合并症。
在 5 年随访的横断面分析中，FP 评估的虚弱与健壮之间的未调整比值比（OR）对于 IL-6（OR：1.56，95%置信区间 [CI]：1.23-1.98）和 IL-8（OR：1.28，95% CI：1.00-1.63）具有显著相关性。在年龄调整（OR：1.58，95% CI：1.21-2.05）和多变量调整模型（OR：1.54，95% CI：1.16-2.05）中，IL-6 仍与 FP 显著相关。在未调整的纵向分析中，IL-8（OR：1.32，95% CI：1.03-1.70）和 IP-10（OR：1.32，95% CI：1.03-1.70）在 5 年时预测 8 年随访时的新发虚弱。IL-8 在年龄后仍与新发虚弱呈纵向相关（OR：1.34，95% CI：1.03-1.75），但在多变量调整后无相关性（OR：1.20，95% CI：0.98-1.70）。FI 也观察到了类似的结果。其他生物标志物与新发虚弱均无显著相关性。
我们的研究结果表明，IL-6 和 IL-8 可能与虚弱具有横断面相关性，而所有测量的炎症生物标志物均与虚弱无因果关系。结合以前的研究，结果表明，虚弱与 IL-6 和 IL-8 特异性相关，而不仅仅代表一种非特异性的全身炎症状态。
