Laboratory of Ageing and Pharmacology, Kolling Institute of Medical Research, Faculty of Medicine and Health, Royal North Shore Hospital, University of Sydney, St Leonards, Sydney, New South Wales, Australia.
Departments of Clinical Pharmacology and Aged Care, Royal North Shore Hospital, St Leonards, Sydney, New South Wales, Australia.
J Gerontol A Biol Sci Med Sci. 2022 Jul 5;77(7):1295-1303. doi: 10.1093/gerona/glac061.
Aging and multimorbidity are associated with inflammation. Polypharmacy is common in older people with multimorbidity. Given the potential for interactions between polypharmacy and inflammation, the relationship between inflammation and polypharmacy were studied in older adults with multimorbidity and in healthy aging mice. A cross-sectional analysis of data from the 5-year wave of the Concord Health and Ageing in Men Project, a population-based study of community-dwelling men aged ≥70 years. Serum concentrations of 27 cytokines were measured using a multiplex immunoassay. Associations between polypharmacy (≥5 medications) and cytokines were evaluated using multivariable linear regression adjusting for age, frailty, comorbidities, and individual drug classes. Interaction between polypharmacy and Drug Burden Index (DBI-drugs with anticholinergic and sedative effects) was analyzed. Effects of polypharmacy and DBI on serum levels of 23 cytokines were determined in aging male mice treated with chronic polypharmacy or control. Compared to the nonpolypharmacy group (n = 495), CHAMP participants with polypharmacy (n = 409) had significantly higher concentrations of IL-8, IL-6, CCL3, Eotaxin, IL-1ra, IL-1β, IP-10, and lower concentrations of anti-inflammatory cytokine IL-4. In fully-adjusted multivariable models, polypharmacy was positively associated with concentrations of IL-8 and CCL3. There were no significant differences in inflammatory profiles between control and polypharmacy-treated mice. The relationship was not influenced by DBI in men or in mice. Inflammatory markers associated with polypharmacy in older adults were not seen in healthy aged mice administered polypharmacy, and may be related to underlying diseases. The polypharmacy mouse model provides opportunities for mechanistic investigations in translational research.
衰老和多种疾病与炎症有关。患有多种疾病的老年人通常会同时服用多种药物。鉴于同时服用多种药物和炎症之间可能存在相互作用，本研究旨在探讨患有多种疾病的老年人和健康衰老的小鼠中炎症与同时服用多种药物之间的关系。这是一项对基于人群的、年龄≥70 岁的社区居住男性的 5 年 Concord 健康与老龄化男性项目（Concord Health and Ageing in Men Project）的第 5 波数据进行的横断面分析。采用多重免疫分析法测定 27 种细胞因子的血清浓度。采用多变量线性回归方法，调整年龄、衰弱、合并症和个体药物类别后，评估同时服用多种药物（≥5 种药物）与细胞因子之间的关系。分析了同时服用多种药物与药物负担指数（DBI-具有抗胆碱能和镇静作用的药物）之间的相互作用。采用慢性同时服用多种药物或对照药物处理衰老雄性小鼠，确定同时服用多种药物和 DBI 对 23 种细胞因子血清水平的影响。与非同时服用多种药物组（n = 495）相比，同时服用多种药物组（n = 409）的 CHAMP 参与者血清中 IL-8、IL-6、CCL3、Eotaxin、IL-1ra、IL-1β、IP-10 的浓度明显更高，抗炎细胞因子 IL-4 的浓度明显更低。在完全调整的多变量模型中，同时服用多种药物与 IL-8 和 CCL3 的浓度呈正相关。对照组和同时服用多种药物组的小鼠的炎症谱无显著差异。在男性和小鼠中，DBI 均未对该关系产生影响。在接受同时服用多种药物治疗的健康衰老小鼠中未观察到与老年人同时服用多种药物相关的炎症标志物，这可能与潜在疾病有关。同时服用多种药物的小鼠模型为转化研究中的机制研究提供了机会。
