Chained mediation of interleukins linking fluoride exposure to frailty: a cohort study of skeletal fluorosis patients in China.

IF 7.3 2区环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES

Environmental Health Pub Date : 2025-12-01 DOI:10.1186/s12940-025-01240-0

Yun Lu, FuYu Tao, Ting Hu, Rourou Wang, Zhijuan Shao, Hongbing Ye, Guanghong Yang, Jingshu Li, Qingzhen Jia, Feng Hong, Peng Luo

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Abstract

Background: Chronic fluorosis, characterized by excessive exposure to fluoride, is associated with a greater risk of frailty in endemic populations. While fluoride correlates with inflammation and frailty, the mediating role of interleukins (ILs) remains unclear. This study investigated the potential multiple mediation pathways of ILs on the relationship between fluoride exposure and frailty in skeletal fluorosis patients.

Methods: A multicenter cross-sectional cohort (N= 678; age: ≥40 years) from high-fluoride areas in China (2023-2024) was enrolled. Urine fluoride (uF) was used to assess exposure. Frailty was measured via the FRAIL scale, and serum ILs (IL-6, IL-8, IL-1β, and IFN-α) were measured via ELISA. Associations and potential mediating pathways were evaluated via chain mediation models (PROCESS macro, SPSS),which test IL-mediated pathways between uF and frailty and adjust for age/sex. Bootstrapping (5,000 resamples) was used to estimate 95% CIs.

Results: Frailty prevalence (5.9%) surpassed that of the general population (2.3%). A high uF value was directly associated with frailty risk (β = 0.2856, P < 0.001). Two potential pathways were identified: the inflammatory cascade: uF→IL-6↑ (β= 0.2947) → IL-1β↑ (β= 0.3936) →frailty (β= 0.0893), and the indirect association accounted for 3.6% of the total effect. Muscle-nutrition depletion: IL-1β↑ → sarcopenia↑ (β= 0.1137)→ increased undernutrition risk↑ (β=-0.2148)→ frailty (β=-0.1990); the indirect association accounted for 4.2% of the total effect. IFN-α attenuated the association of fluoride with IL-1β (P = 0.0113) and was linked to lower frailty risk (β = -0.086, P < 0.01). CONCLUSIONS : The"IL-6→IL-1β" pathway is a potential mechanism for inflammation-related frailty, and nutritional interventions could disrupt the "IL-1β→sarcopenia→malnutrition" cycle. IFN-α has a protective effect on fluoride-induced inflammation.

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氟化物暴露与虚弱之间白介素的链式中介作用：中国氟骨症患者的队列研究

背景：慢性氟中毒以过度接触氟化物为特征，在地方性人群中与更大的虚弱风险相关。虽然氟化物与炎症和虚弱有关，但白细胞介素（il）的介导作用尚不清楚。本研究探讨了白介素在氟骨症患者氟暴露与虚弱之间可能的多重介导途径。方法：选取2023-2024年中国高氟地区的多中心横断面队列（N= 678，年龄≥40岁）。尿氟化物（uF）被用来评估暴露。采用虚弱量表检测各组患者的虚弱程度，ELISA法检测各组血清IL-6、IL-8、IL-1β、IFN-α水平。通过链式中介模型（PROCESS macro， SPSS）评估关联和潜在的中介途径，该模型测试il介导的uF和虚弱之间的途径，并根据年龄/性别进行调整。使用Bootstrapping（5,000个样本）来估计95%的ci。结果：虚弱患病率（5.9%）高于普通人群（2.3%）。高uF值与脆弱风险直接相关（β = 0.2856, P < 0.001）。发现两种潜在通路：炎症级联：uF→IL-6↑（β= 0.2947）→IL-1β↑（β= 0.3936）→虚弱（β= 0.0893），间接关联占总效应的3.6%。肌肉营养耗损：IL-1β↑→肌肉减少症↑（β= 0.1137）→营养不良风险增加↑（β=-0.2148）→虚弱（β=-0.1990）；间接关联占总影响的4.2%。IFN-α降低了氟化物与IL-1β的相关性（P = 0.0113），并与降低虚弱风险相关（β = -0.086, P < 0.01）。结论：“IL-6→IL-1β”通路是炎症相关虚弱的潜在机制，营养干预可破坏“IL-1β→肌肉减少→营养不良”循环。IFN-α对氟化物引起的炎症有保护作用。

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来源期刊

Environmental Health 环境科学-公共卫生、环境卫生与职业卫生

CiteScore

10.10

自引率

1.70%

发文量

115

审稿时长

3.0 months

期刊介绍： Environmental Health publishes manuscripts on all aspects of environmental and occupational medicine and related studies in toxicology and epidemiology. Environmental Health is aimed at scientists and practitioners in all areas of environmental science where human health and well-being are involved, either directly or indirectly. Environmental Health is a public health journal serving the public health community and scientists working on matters of public health interest and importance pertaining to the environment.