Science Inventory

Linking physiological parameters to perturbations in the human exposome: Environmental exposures modify blood pressure and lung function via inflammatory cytokine pathway

Citation:

Stiegel, M., J. Pleil, J. Sobus, T. Stevens, AND M. Madden. Linking physiological parameters to perturbations in the human exposome: Environmental exposures modify blood pressure and lung function via inflammatory cytokine pathway. JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH - PART A: CURRENT ISSUES. Taylor & Francis, Inc., Philadelphia, PA, 80(9):485-501, (2017).

Impact/Purpose:

In the short term, human health effects from environmental chemicals and stressors are subtle, but small biological changes are thought to accrue over a lifetime of insults and overwhelm cellular, tissue, and DNA repair functions resulting in various human disease types including cancer, autoimmune, neurological, and cardiovascular. This concept has been developed over the past decade within the construct of the human exposome proposed by Christopher Wild (2005). More recently, Stephen Rappaport and Martyn Smith have proposed that “…70 to 90% of disease risks are probably due to differences in environments.” essentially implicating the genetic interaction with the environment (G x E) as the causative agent (Rappaport and Smith, 2010).

Description:

Human biomonitoring is an indispensable tool for establishing the systemic effects from external stressors including environmental pollutants, chemicals from consumer products, and pharmaceuticals. This article uses a combination of new results and meta-data from previous work to explore environmental exposures to diesel exhaust (DE) and ozone (O3) and interpret these parameters from the perspective of in vitro to in vivo extrapolation. The ultimate goal is to use cytokine expression at the cellular level as a biomarker for physiological systemic responses such as blood pressure and lung function. This study investigates human co- exposures to combinations of DE and O3 and the response correlations between forced exhaled volume in 1 second (FEV1), forced vital capacity (FVC), systolic and diastolic blood pressure (SBP and DBP,respectively), and 10 inflammatory cytokines (interleukins 1β, 2, 4, 5, 8, 10, 12p70 and 13, IFN-γ, and TNF-α) for 15 healthy human volunteers. DE exposure demonstrated a significant negative Spearman correlation between the Th1 cytokine IL-12p70 and DBP (ρ=-0.529). The O3 exposure results showed a negative DBP correlation with the Th2 cytokine IL-5 (ρ=-0.546).Significant positive correlations were found between IFN-γ and both FEV1 (ρ=0.843) and FVC (ρ=0.711) for the O3 exposure. Although the DE+O3 co-exposure results had no globally statistically significant correlations between cytokines or blood pressure values with lung function measurements, results showed that SBP had strong negative correlations with both IL-8(ρ=-0.675) and IFN-γ (ρ=-0.729). Results across all exposures revealed that certain individuals had a much greater inflammatory response compared to the group and, generally, there was more between-person variation in the response; individuals are more stable within themselves and are more likely to have responses independent of one another. Stratification of these responses by GSTM1 genotype did not elucidate any underlying patterns. This work suggests that in vitro work could be implemented to help elucidate the underlying mechanistic pathways observed in this study and to ultimately serve as part of an adverse outcome pathway (AOP) for linking high-throughput toxicity tests to physiological in vivo responses.

URLs/Downloads:

http://dx.doi.org/10.1080/15287394.2017.1330578   Exit

Record Details:

Record Type: DOCUMENT (JOURNAL/PEER REVIEWED JOURNAL)
Product Published Date: 09/01/2017
Record Last Revised: 09/07/2017
OMB Category: Other
Record ID: 337527

Organization:

U.S. ENVIRONMENTAL PROTECTION AGENCY

OFFICE OF RESEARCH AND DEVELOPMENT

NATIONAL EXPOSURE RESEARCH LABORATORY

EXPOSURE METHODS & MEASUREMENT DIVISION