Do urinary metals associate with the homeostasis of inflammatory mediators? Results from the perspective of inflammatory signaling in middle-aged and older adults

Abstract

Objective: We aimed to investigate whether urinary metal mixtures are associated with the homeostasis of inflammatory mediators in middle-aged and older adults.

Methods: A four-visit repeated-measures study was conducted with 98 middle-aged and older adults from five communities in Beijing, China. Only one person was lost to follow-up at the third visit. Ultimately, 391 observations were included in the analysis. The urinary concentrations of 10 metals were measured at each visit using inductively coupled plasma mass spectrometry (ICP-MS) with a limit of detection (LOD) ranging from 0.002 to 0.173 µg/L, and the detection rates were all above 84%. Similarly, 14 serum inflammatory mediators were measured using a Beckman Coulter analyzer and the Bio-Plex MAGPIX system. A linear mixed model (LMM), LMM with least absolute shrinkage and selection operator regularization (LMMLASSO), and Bayesian kernel machine regression (BKMR) were adopted to explore the effects of urinary metal mixtures on inflammatory mediators.

Results: In LMM, a two-fold increase in urinary cesium (Cs) and chromium (Cr) was statistically associated with -35.22% (95% confidence interval [CI]: -53.17, -10.40) changes in interleukin 6 (IL-6) and -11.13% (95 %CI: -20.67, -0.44) in IL-8. Urinary copper (Cu) and selenium (Se) was statistically associated with IL-6 (88.10%, 95%CI: 34.92, 162.24) and tumor necrosis factor-alpha (TNF-α) (22.32%, 95%CI: 3.28, 44.12), respectively. Similar results were observed for the LMMLASSO and BKMR. Furthermore, Cr, Cs, Cu, and Se were significantly associated with other inflammatory regulatory network mediators. For example, urinary Cs was statistically associated with endothelin-1, and Cr was statistically associated with endothelin-1 and intercellular adhesion molecule 1 (ICAM-1). Finally, the interaction effects of Cu with various metals on inflammatory mediators were observed.

Conclusion: Our findings suggest that Cr, Cs, Cu, and Se may disrupt the homeostasis of inflammatory mediators, providing insight into the potential pathophysiological mechanisms of metal mixtures and chronic diseases.

Keywords: Bayesian kernel machine regression; Mediator homeostasis; Middle-aged and older adults; Repeated measurement; Urinary metal mixtures.