2023 FDA Science Forum
Sex-based differences in inflammasome activation due to silver nanoparticles
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Contributing OfficeNational Center for Toxicological Research
Abstract
It has been increasingly important to distinguish sex when evaluating the biocompatibility of nanomaterials. Increasing evidence has been reported demonstrating the distinguishable differences in male and female innate and adaptive immune systems. Silver nanoparticles (AgNPs) have been incorporated into consumer, healthcare, and industrial products to serve as an anti-microbial agent. However, emerging health concerns involving continuous exposure to these AgNPs have been associated to reports demonstrating the proinflammatory and toxic effects of AgNPs. To date, the effects of AgNPs on the basic immunological functions have not been thoroughly evaluated to compare the potential sex-based differences. Thus, the goal of the study aims to investigate the sex-based differences in inflammasome activation after exposure to AgNPs on peripheral blood mononuclear cells (PBMCs) from 6 male and 6 female healthy human donors. These PBMCs were obtained from younger donors (ages 20 – 30 years old) and older donors (ages 40 – 51 years old) for comparison purposes. AgNPs (30 nm) were characterized for their hydrodynamic size by dynamic light scattering and their primary size by transmission electron microscopy. PBMCs were exposed to AgNPs (30 nm) for a period of 6- and 24-hours. Following exposure, IL-1β was monitored by ELISA to determine the inflammasome activity. The 6-hour exposure to AgNPs cause significantly more inflammasome activation in the females. This induction was still observed after 24-hours but was determined not be statistically significant. The young males had more inflammasome activity after 6-hours when compared to the old males; however, this difference was not observed after 24-hours. Interestingly, both age groups had similar inflammasome activation after 6-hours, but the young females had more inflammasome activity after the 24-hour exposure than the older females. The results demonstrate a distinct sex- and age-based difference in inflammasome activation by AgNPs. These findings provide more information that may help evaluating the potential sex-based health risks associated with AgNPs for improving women’s and men’s health.
