An Exposure Study Linking Environmental and Human Biological Parameter Measurements, with a Focus on Th1/Th2 Cytokine Expression
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Stiegel, Matthew. An Exposure Study Linking Environmental and Human Biological Parameter Measurements, with a Focus On Th1/th2 Cytokine Expression. Chapel Hill, NC: University of North Carolina at Chapel Hill Graduate School, 2014. https://doi.org/10.17615/ztej-bb59APA
Stiegel, M. (2014). An Exposure Study Linking Environmental and Human Biological Parameter Measurements, with a Focus on Th1/Th2 Cytokine Expression. Chapel Hill, NC: University of North Carolina at Chapel Hill Graduate School. https://doi.org/10.17615/ztej-bb59Chicago
Stiegel, Matthew. 2014. An Exposure Study Linking Environmental and Human Biological Parameter Measurements, with a Focus On Th1/th2 Cytokine Expression. Chapel Hill, NC: University of North Carolina at Chapel Hill Graduate School. https://doi.org/10.17615/ztej-bb59- Last Modified
- March 19, 2019
- Creator
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Stiegel, Matthew
- Affiliation: Gillings School of Global Public Health, Department of Environmental Sciences and Engineering
- Abstract
- Diesel exhaust (DE) and ozone (O3) inhalation exposures are both recognized for creating, or exacerbating, cardiopulmonary health effects in humans. The U.S. Environmental Protection Agency (EPA) has regulations described in the National Ambient Air Quality Standards (NAAQS) that establish ambient standards for O3 and for some of the constituents of DE, including particulate matter, carbon monoxide, nitrogen oxides and sulfur oxides, but there are no regulations that include all components of DE emissions. While there is scientific evidence for exposure-related health effects from DE and O3 separately, there is little research investigating co-exposures to these two pollutants. To address this data gap, this dissertation explores the human inflammatory response as an early indicator for exposures sufficient for activating the immune system with a series of highly-controlled environmental chamber studies. Healthy human subjects were exposed to clean filtered air, DE, O3, and DE+O3 at typical urban air concentrations. A multiplex immunochemistry method was used to analyze the Th1/Th2 inflammatory cytokines: interleukins (1beta, 2, 4, 5, 8, 10, 12p70 and 13), interferon-gamma, and tumor necrosis factor-alpha, in human blood, breath and urine samples. In addition, health outcome parameters for cardiopulmonary function (systolic/diastolic blood pressure, forced exhaled volume in 1 second, and forced vital capacity) were measured. The results demonstrated sufficient sensitivity for characterizing all 10 cytokines at levels of 0.05-0.10 pg/ml with a dynamic range up to 100 ng/ml. Specific cytokines responded to the DE-only and O3-only exposures, and a synergistic relationship was found as a suppression (lasting as long as 22 hrs) of IL-5, IL-12p70, IFN-gamma, and TNF-alpha after DE + O3 co-exposure. Varieties of relationships were explored between subject meta-data and physiological (cardiopulmonary) observations, which demonstrated high exposure-response variability between individuals and that summary data can mask certain underlying relationships. The overall results suggest that O3 exposure is highly correlated with decreased pulmonary function, that Th1-mediated inflammation is a moderator between DE+O3 exposure and post-exposure blood pressure modifications, and that epidemiologically observed associations between environmental exposures and cardiopulmonary effects are mediated by inflammatory response mechanisms.
- Date of publication
- December 2014
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- In Copyright
- Advisor
- Pleil, Joachim
- Fry, Rebecca
- Madden, Michael
- Waidyanatha, Suramya
- Leith, David
- Flynn, Michael
- Truong, Young
- Degree
- Doctor of Philosophy
- Degree granting institution
- University of North Carolina at Chapel Hill Graduate School
- Graduation year
- 2014
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- Place of publication
- Chapel Hill, NC
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- There are no restrictions to this item.
- Date uploaded
- April 23, 2015
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