Use of Generalized Weighted Quantile Sum Regressions of Tumor Necrosis Factor Alpha and Kidney Function to Explore Joint Effects of Multiple Metals in Blood

Exposure to heavy metals could lead to adverse health effects by oxidative reactions or inflammation. Some essential elements are known as reactors of anti-inflammatory enzymes or coenzymes. The relationship between tumor necrosis factor alpha (TNF-alpha) and heavy metal exposures was reported. However, the interaction between toxic metals and essential elements in the inflammatory response remains unclear. This study aimed to explore the association between arsenic (As), cadmium (Cd), lead (Pb), cobalt (Co), copper (Cu), selenium (Se), and zinc (Zn) in blood and TNF-alpha as well as kidney function. We enrolled 421 workers and measured the levels of these seven metals/metalloids and TNF-alpha in blood; kidney function was calculated by CKD-EPI equation. We applied weighted quantile sum (WQS) regression and group WQS regression to assess the effects of metal/metalloid mixtures to TNF-alpha and kidney function. We also approached the relationship between metals/metalloids and TNF-alpha by generalized additive models (GAM). The relationship of the exposure-response curve between Pb level and TNF-alpha in serum was found significantly non-linear after adjusting covariates (p < 0.001). Within the multiple-metal model, Pb, As, and Zn were associated with increased TNF-alpha levels with effects dedicated to the mixture of 50%, 31%, and 15%, respectively. Grouped WQS revealed that the essential metal group showed a significantly negative association with TNF-alpha and kidney function. The toxic metal group found significantly positive associations with TNF-alpha, serum creatinine, and WBC but not for eGFR. These results suggested Pb, As, Zn, Se, and mixtures may act on TNF-alpha even through interactive mechanisms. Our findings offer insights into what primary components of metal mixtures affect inflammation and kidney function during co-exposure to metals; however, the mechanisms still need further research.

Automated summary

Exposure to heavy metals can have negative health effects due to oxidative reactions or inflammation. This study explores the association between arsenic, cadmium, lead, zinc, selenium, and TNF-alpha as well as kidney function.