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. 2016 Apr 8;11(4):e0152458.
doi: 10.1371/journal.pone.0152458. eCollection 2016.

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

Matthew A Stiegel  1 , Joachim D Pleil  2 , Jon R Sobus  2 , Michael C Madden  3
Affiliations

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

Matthew A Stiegel et al. PLoS One. .

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.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Exposure schedule for volunteers.Each exposure arm is composed of three days.
Day 1 is one of the four exposures (clean air, DE, O3, or DE+O3), Day 2 is always O3, and Day 3 has no exposure.
Fig 2
Fig 2. Heatmap of the plasma cytokine levels for all exposure treatments over a 24-hour period. The concentrations in Fig 2 increase as the color changes from blue to red.
Fig 3
Fig 3. Post/Pre exposure cytokine concentration ratios for the four treatments.
Each blue “dot” represents an individual Post/Pre cytokine concentration ratio for that respective treatment. A solid line in each of the cytokine scatterplots displays the median post/pre ratio. The dotted line that is anchored at “1” on each y-axis indicates the ratio where the Pre-exposure concentration is equal to the Post-exposure concentration. A statistically significant result above/below “1” indicates that there has been an increase/decrease in the concentration for that respective cytokine at end of the 2-hour exposure period.
Fig 4
Fig 4. Follow-up/Pre exposure cytokine concentration ratios for the four treatments.
Each blue “dot” represents an individual Follow-up/Pre cytokine concentration ratio for that respective treatment. A solid line in each of the cytokine scatterplots displays the median follow-up/pre ratio. The dotted line that is anchored at “1” on each y-axis indicates the ratio where the Pre-exposure concentration is equal to the Follow-up concentration. A statistically significant result above “1” indicates that there has been an increase in the concentration for that respective cytokine 22-hours after the end of the 2-hour exposure period. A statistically significant result below “1” indicates that there has been a decrease in the concentration for that respective cytokine 22-hours after the end of the 2-hour exposure period.
Fig 5
Fig 5. TNF-α cytokine results for three exposure scenarios.
The boxes in Fig 5, above, display the median, upper 75%, and lower 25% of the concentrations for TNF-α, while the bars display the upper 97.5% and the lower 2.5% of the concentrations. This figure shows that the combination of the DE-only and O3-only exposures into a DE+O3 co-exposure creates a suppression of TNF-α that does not recover after a 22-hour period.
Fig 6
Fig 6. Spearman correlations for pre, post and 22-hour post DE+O3 co-exposure responses.A white dot in a cell indicates a statistically significant (p<0.05) positive or negative correlation.
Lymph = lymphocytes, Mono = monocytes, PMN = polymorphonuclear neutrophil.
See this image and copyright information in PMC

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