Relations of urinary volatile organic compound metabolites with inflammation and immune response

Background and Aim: Volatile organic compounds (VOCs) are ubiquitous environmental pollutants that are generated by combustion, industrial solvents, and household items. VOCs are also detected at several hazardous waste sites. Exposure to VOCs is associated with insulin resistance, diabetes, and cardiovascular disease. However, the effects of VOCs on systemic inflammation are unclear. We evaluated the relation of urinary VOC metabolites, individually and in mixtures, with circulating cytokines and immune cells in a cross-sectional study of 625 participants (ages 25-70 years) from Louisville, Kentucky, USA. Methods: We quantified a) concentrations of 16 urinary metabolites corresponding to 12 parent VOCs by liquid chromatography-mass spectrometry; b) blood immune cells by blood analyzer; and c) plasma cytokines by multiplex array. Using linear regression models, we estimated covariate-adjusted relations of individual VOC metabolites with ln-transformed cytokine concentrations and immune cells. We used quantile-based g-computation to estimate covariate-adjusted relations of urinary VOC metabolite mixtures with inflammation biomarkers. Results: We found weak to moderate positive correlations between cytokines, correlation coefficients ranged from 0.03 to 0.59. In separate models, interquartile range (IQR) increases in the urinary metabolites of crotonaldehyde, acrylonitrile, 1,3-butadiene, and acrolein were associated with 4.0 to 10% higher concentrations of several pro-inflammatory cytokines, including IL-6, IL-8, or MCP1. Higher concentrations of the propylene oxide metabolite were associated with lower IL-9 (-1.0% per IQR; 95%CI=-1.1, -0.1). In mixture analyses, a quartile increase in all VOC metabolites was associated with 8.6% (-15, -2.0%) lower IL-10, an anti-inflammatory cytokine, and 5.1% (95% CI= 1.0, 11%) higher white blood cell count. These associations were largely driven by acrylonitrile and 1,3 butadiene, respectively. We did not find strong evidence of a joint VOC mixture effect on IL-6, IL-8, or MCP1. Conclusions: VOC exposure could promote systemic inflammation thereby increasing susceptibility to cardiometabolic disease. Keywords: volatile organic compounds, chemical mixtures, inflammation, cytokines