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O6D.4 Association of occupational exposures with ex vivo functional immune response in workers handling carbon nanotubes and nanofibers
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  1. Mary Schubauer-Berigan1,2,
  2. Matthew Dahm2,
  3. John Beard3,
  4. Vamsi Kodali4,
  5. Patti Zeidler-Erdely4,
  6. Aaron Erdely4
  1. 1International Agency for Research on Cancer, Lyon, France
  2. 2National Institute for Occupational Safety and Health, Cincinnati, USA
  3. 3Brigham Young University, Provo, USA
  4. 4National Institute for Occupational Safety and Health, Morgantown, USA

Abstract

Animal toxicology studies suggest that workers exposed to carbon nanotubes or nanofibers (CNT/F) may experience pulmonary or systemic health effects; however, direct human evidence is lacking. Our study’s objective was to evaluate associations between CNT/F exposure and ex vivo responses of leukocytes challenged with secondary stimulants, adjusting for potential confounders, in a cross-sectional study. We measured multi-day exposure using CNT/F structure count (SC) and elemental carbon air concentrations among 102 U.S. workers. Demographic, lifestyle, and other occupational information was obtained via in-person interview. Workers’ whole blood was incubated for 18 hours with and without two microbial stimulants (lipopolysaccharide and staphylococcal enterotoxin type B) using TruCulture® technology to evaluate immune cell activity. Following incubation, collected supernatants were preserved and subsequently analyzed for cytokine and chemokine concentrations. The ratio of stimulant:null response for each protein was analyzed using multiple linear regression, principal components (PC) analysis, and Ingenuity® Pathway Analysis (IPA) to determine whether patterns of protein response were associated with CNT/F exposure. We found that CNT/F metrics (most consistently, the SC-based) were significantly (p<0.05) inversely associated with stimulant:null ratios of GM-CSF, IFN-γ, interleukin (IL)−2, IL-4, IL-5, IL-10, IL-17, and IL-23. CNT/F metrics were significantly inversely associated with PC1 (a weighted mean of most biomarkers that explained 25% of the variance in the set of protein ratios) and PC2 (a biomarker contrast that explained 14%). Among other occupational exposures, only solvent exposure was significantly (and was inversely) related to PC2. IPA suggested a CNT/F-associated generalized inhibition of all leukocyte responses when challenged with a secondary stimulus. We found that CNT/F exposure metrics were uniquely related to a pattern of reduced stimulant responses in challenged circulating leukocytes. This approach, if replicated in other exposed populations, may present a relatively sensitive method to evaluate human response to CNT/F or other occupational exposures.

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