Inflammatory Cytokines and White Blood Cell Counts Response to Environmental Levels of Diesel Exhaust and Ozone Inhalation Exposures

Abstract

Epidemiological observations of urban inhalation exposures to diesel exhaust (DE) and ozone (O3) have shown pre-clinical cardiopulmonary responses in humans. Identifying the key biological mechanisms that initiate these health bioindicators is difficult due to variability in environmental exposure in time and from person to person. Previously, environmentally controlled human exposure chambers have been used to study DE and O3 dose-response patterns separately, but investigation of co-exposures has not been performed under controlled conditions. Because a mixture is a more realistic exposure scenario for the general public, in this study we investigate the relationships of urban levels of urban-level DE exposure (300 μg/m3), O3 (0.3 ppm), DE + O3 co-exposure, and innate immune system responses. Fifteen healthy human volunteers were studied for changes in ten inflammatory cytokines (interleukins 1β, 2, 4, 5, 8, 10, 12p70 and 13, IFN-γ, and TNF-α) and counts of three white blood cell types (lymphocytes, monocytes, and neutrophils) following controlled exposures to DE, O3, and DE+O3. The results show subtle cytokines responses to the diesel-only and ozone-only exposures, and that a more complex (possibly synergistic) relationship exists in the combination of these two exposures with suppression of IL-5, IL-12p70, IFN-γ, and TNF-α that persists up to 22-hours for IFN-γ and TNF-α. The white blood cell differential counts showed significant monocyte and lymphocyte decreases and neutrophil increases following the DE + O3 exposure; lymphocytes and neutrophils changes also persist for at least 22-hours. Because human studies must be conducted under strict safety protocols at environmental levels, these effects are subtle and are generally only seen with detailed statistical analysis. This study indicates that the observed associations between environmental exposures and cardiopulmonary effects are possibly mediated by inflammatory response mechanisms.

Traffic‐related air pollution induces non‐allergic eosinophilic airway inflammation and cough hypersensitivity in guinea‐pigs

“…This is in part comparable to a laboratory‐based exposure study in which mice intratracheally instilled with motorcycle exhaust particles induced a Th2 response and airway eosinophilia . In addition, our findings are consistent with numerous previous studies showing increased overall inflammation including neutrophilia in the airways of experimental animals and humans following TRAP exposure.…”

Nanotoxicology: The Need for a Human Touch?

“…These include localized effects such as bronchoconstriction and increased airway resistance, [ 23,50,51 ] pulmonary inflammation, [ 23,52–59 ] and oxidative stress, [ 50,55,60 ] DNA methylation in bronchial biopsies or blood cells, [ 61,62 ] and exacerbation of allergic responses [ 63 ] as well as reductions in parameters related to exercise capacity. [ 64 ] Systemic effects have also been analyzed such as inflammation [ 52,65–67 ] and oxidative stress, [ 68–70 ] increased levels of circulating oxidized lipoprotein receptors, [ 71 ] increased blood pressure, [ 72 ] impaired vascular function (arterial contraction), [ 73,74 ] reduced vasodilator responses, [ 75–79 ] increased arterial stiffening, [ 80 ] promotion of blood clotting, [ 69,81 ] and increased cardiac ischaemia [ 82 ] ( Figure ). Experiments that removed the particulate fraction of DE using experimental filtering or exhaust particle traps [ 83,84 ] demonstrated that it was the particulate constituents of DE that drive cardiovascular impairments.…”

Epigenetic Applications in Adverse Outcome Pathways and Environmental Risk Evaluation

“…In essence, sample source and cell type heterogeneity (i.e., human genetic heterogeneity) are problematic in epigenomic studies because human samples often consist of blood (owing to ease of access) that is composed of mixed cell types. Each cell type has a unique epigenetic profile, and the relative proportion of each cell type in a sample may vary as a result of exposure ( Stiegel et al. 2016 ).…”