Comparison of silver nanoparticle-induced inflammatory responses between healthy and metabolic syndrome mouse models

Silver nanoparticles (AgNPs) are utilized in surgical implants and medical textiles, thus providing access to the circulation. While research has been conducted primarily in healthy models, AgNP-induced toxicity evaluations in disease conditions are critical, as many individuals have preexisting conditions. Specifically, over 20% of United States adults suffer from metabolic syndrome (MetS). It was hypothesized that MetS may increase susceptibility to AgNP-mediated toxicity due to induction of differential inflammation and altered biodistribution. Mice were injected with 2 mg/kg AgNPs, and organs assessed for inflammatory gene expression (TNF-alpha, CXCL1, CXCL2, CCL2, TGF-beta, HO-1, IL-4, IL-13), and Ag content. AgNPs were determined to induce differential inflammation in healthy and MetS mice. While AgNP exposure increased TNF-alpha, CXCL1, TGF-beta, HO-1, and IL-4 expression within healthy mouse spleens, MetS-treated animals demonstrated decreased CXCL1, IL-4, and IL-13 expression. Healthy and MetS mice livers exhibited similar inflammatory responses to one another. AgNPs localized primarily to the liver and spleen, although Ag was present in all examined organs. In organs of minor AgNP deposition, such as kidney, gene expression was variable. Induction of inflammatory genes did not correspond with biodistribution, suggesting disease-related variations in AgNP-mediated adverse responses. These findings indicate that disease may influence inflammation and biodistribution, impacting AgNP clinical applications.