Abstract
Epidemiological studies have suggested associations between polycyclic aromatic hydrocarbons (PAHs) and heart rate variability (HRV). However, the roles of plasma cytokines in these associations are limited. In discovery stage of this study, we used Human Cytokine Antibody Arrays to examine differences in the concentrations of 280 plasma cytokines between 8 coke-oven workers and 16 community residents. We identified 19 cytokines with significant different expression (fold change ≥2 or ≤−2, and q-value <5%) between exposed workers and controls. 4 cytokines were selected to validate in 489 coke-oven workers by enzyme-linked immunosorbent assays in validation stage. We found OH-PAHs were inversely associated with brain-derived neurotrophic factor (BDNF) (p < 0.05), and interquartile range (IQR) increases in OH-PAHs were associated with >16% BDNF decreases. Additionally, OH-PAHs were positively associated with activated leukocyte cell adhesion molecule (ALCAM) and C-reactive protein (CRP) (p < 0.05), and IQR increases in OH-PAHs were associated with >20% increases in CRP. We also found significant associations between these cytokines and HRV (p < 0.05), and IQR increases in BDNF and CRP were associated with >8% decreases in HRV. Our results indicated PAH exposure was associated with plasma cytokines, and higher cytokines were associated with decreased HRV, but additional human and potential mechanistic studies are needed.
Highlights
The increase in fossil fuel-based energy production has led to massive amounts of fine particulate matter (≤ 2.5 μ m in aerodynamic diameter; PM2.5) air pollution
Our pilot study has examined the associations of polycyclic aromatic hydrocarbons (PAHs) exposure with one candidate cytokine—IL-6, and of IL-6 with heart rate variability (HRV) indices, and found that IL-6 might play an important role in PAH-induced cardiac autonomic dysfunction[17]
We followed a serial of selection criteria and selected 4 marked cytokines for validation from these 19 differentially expressed cytokines: brain-derived neurotrophic factor (BDNF), activated leukocyte cell adhesion molecule (ALCAM), C-reactive protein (CRP), and macrophage stimulating protein (MSP) (Table 2)
Summary
The increase in fossil fuel-based energy production has led to massive amounts of fine particulate matter (≤ 2.5 μ m in aerodynamic diameter; PM2.5) air pollution. Recent epidemiologic studies consistently suggested PAH exposure is associated with elevated risks of cardiovascular diseases (CVDs)[4,5]. Epidemiological studies, including those from our lab, have indicated that PAH exposure is associated with decreased heart rate variability (HRV)[6,7,8], an established marker of cardiac autonomic dysfunction and PM-mediated cardiovascular events and mortality[9,10]. Most existing epidemiological studies just have assessed associations between inflammatory markers and particulate air pollution as a whole mixture instead of specific constituents or internal exposure. In the present study, we undertook a two-stage study to identify PAH-associated plasma cytokines and explore their associations with HRV through: a) comparing the cytokine expression profiles between different PAHs exposure groups using cytokine antibody array; b) validating several differentially expressed cytokines and evaluating their associations with PAH exposure; and c) assessing the associations between the PAH-associated cytokines and HRV
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