Article Text
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.