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Inflammatory Cytokines as Preclinical Markers of Adverse Responses to Chemical Stressors
Citation:
Angrish, M., M. Madden, AND J. Pleil. Inflammatory Cytokines as Preclinical Markers of Adverse Responses to Chemical Stressors. PittCon 2015, New Orleans, LA, March 08 - 12, 2015.
Impact/Purpose:
The National Exposure Research Laboratory (NERL) Human Exposure and Atmospheric Sciences Division (HEASD) conducts research in support of EPA mission to protect human health and the environment. HEASD research program supports Goal 1 (Clean Air) and Goal 4 (Healthy People) of EPA strategic plan. More specifically, our division conducts research to characterize the movement of pollutants from the source to contact with humans. Our multidisciplinary research program produces Methods, Measurements, and Models to identify relationships between and characterize processes that link source emissions, environmental concentrations, human exposures, and target-tissue dose. The impact of these tools is improved regulatory programs and policies for EPA.
Description:
Abstract: The in vivo cytokine response to chemical stressors is a promising mainstream tool used to assess potential systemic inflammation and immune function changes. Notably, new instrumentation and statistical analysis provide the selectivity and sensitivity to rapidly differentiate and quantify inflammatory and allergy-related cytokines from small amounts of sample, and contrast baseline with exposure response cytokine levels. The cytokine profiles of several species are currently being examined for connections to the molecular pathways involved in adverse events. The molecular-adverse effect link is critical to identify key adverse outcome pathways (AOPs) that are used for risk assessment. Cytokine profiles have the potential to bridge the cross-species gap by translating results from invasive animal studies of AOPs to the human response. Meso Scale Discovery (MSD) MULTI-ARRAY® multiplex sandwich immuno-assays enabled ultra-sensitive cytokine quantitation of a minimal sample amount isolated from controlled exposure studies with rodents or human blood, urine, and exhaled breath condensate. Statistical analyses of sample distribution, variation, and correlation link the species gap and allow cross-species comparisons between cytokine responses. This rapid and robust approach will lay the groundwork for building AOPs from an expanding portfolio of registered and emerging chemicals.