青春发育早期的混合金属暴露可能增加青少年系统性炎症指数升高的风险

Associations between serum metal mixtures and systemic inflammation indices among Chinese early adolescents: A prospective cohort study

中国青春发育早期青少年的血清混合金属暴露与系统性炎症指数的关联：一项前瞻性队列研究

Authors：Yonghan Li, Binbin Huang, Mengyuan Yuan, Chao Zhang, Xueying Zhang, Jiahu Hao, Fangbiao Tao, Feng Geng, Gengfu Wang, Puyu Su

Source：Ecotoxicology And Environmental Safety 

PMID: 40014987

DOI: 10.1016/j.ecoenv.2025.117952

Abstract

Background: Research has demonstrated a link between metal exposure and inflammation. However, little is known about this relationship among adolescents, especially in prospective cohort studies. The aim of this study was to investigate the relationship between serum metal exposure and inflammatory status in Chinese early adolescents.

Methods: In this study, 12 serum metals were detected at baseline in 1551 participants from the Chinese Early Adolescents Cohort. The participants' inflammatory status was assessed via three systemic inflammation indices (neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII)) at both baseline and follow-up. Generalized linear mixed models and restricted cubic splines regression were used to examine the linear and nonlinear relationships between single metal concentrations and systemic inflammation indices. Multiple mixture models were implemented to assess the relationships of mixed metals with systemic inflammation indices. Additionally, sex subgroup analyses were conducted to explore the sex-specific associations between serum metals and inflammatory status.

Results: Single-exposure analysis revealed that exposure to multiple serum metals, such as chromium, cobalt, copper and lead, was positively associated with the NLR and SII, whereas iron was negatively correlated with the three systemic inflammation indices (PFDR<0.05). Additionally, inverted U-shaped associations were observed between vanadium, manganese and systemic inflammation indices. According to the mixture models, high levels of the serum metal mixture were positively correlated with the NLR and the SII. Cobalt had the highest positive weight in the mixed samples, whereas iron had the greatest negative weight in the serum-metal mixtures. Subgroup analyses revealed that serum exposure to the metal mixture had a more significant effect on systemic inflammation markers in females than in males.

Conclusions: This study reveals the impact of real-world mixed metal exposure on adolescents' inflammatory levels, which is of primary significance for protecting the healthy development of early adolescents.

Keywords: Cobalt; Combined effect; Early adolescents; Iron; Metal mixtures; Systemic inflammation indices.

摘要

背景：研究表明金属暴露与炎症之间存在关联。然而，其在青少年人群中的关联尚不清楚，尤其是在前瞻性队列研究中。本研究旨在探讨中国青春发育早期青少年的血清金属暴露与炎症状态之间的关联。

方法：本研究中，来自中国早期青少年队列的1551名参与者在基线时检测了12种血清金属。在基线和随访时，通过3种系统性炎症指数（中性粒细胞与淋巴细胞比值（NLR）、血小板与淋巴细胞比值（PLR）和全身免疫炎症指数（SII））评估参与者的炎症状态。使用广义线性混合模型和限制性立方样条回归分析单一金属浓度与系统性炎症指数之间的线性和非线性关联。采用多种混合模型评估混合金属暴露与系统性炎症指数的关系。此外，还通过性别亚组分析探索血清金属暴露与炎症状态之间关联的性别特异性。

结果：单金属暴露分析显示，多种血清金属如铬、钴、铜和铅，与NLR和SII水平呈正相关，而铁与3种系统性炎症指数呈负相关（P_FDR <0.05）。此外，钒、锰和系统性炎症指数水平之间观察到倒U形关联。混合模型结果显示，高浓度的血清金属混合暴露与NLR和SII水平呈正相关。钴在混合金属中具有最高的正向权重，而铁在血清金属混合物中的负权重最大。性别亚组分析显示，血清金属混合暴露对女性系统性炎症标志物的影响比男性更为显著。

结论：本研究揭示了真实世界中混合金属暴露对青少年炎症水平的影响，这对促进青春发育早期青少年的健康发展具有重要意义。

关键词：钴；联合效应；青少年早期；铁；金属混合物；系统炎症指数