Cytokines as biomarkers of nanoparticle immunotoxicity

Abstract

Nanoscale objects, whether of biologic origin or synthetically created, are being developed into devices for a variety of bionanotechnology diagnostic and pharmaceutical applications. However, the potential immunotoxicity of these nanomaterials and mechanisms by which they may induce adverse reactions have not received sufficient attention. Nanomaterials, depending on their characteristics and compositions, can interact with the immune system in several ways and either enhance or suppress immune system function. Cytokines perform pleiotropic functions to mediate and regulate the immune response and are generally recognized as biomarkers of immunotoxicity. While the specificity and validity of certain cytokines as markers of adverse immune response has been established for chemicals, small and macromolecular drugs, research on their applicability for predicting and monitoring the immunotoxicity of engineered nanomaterials is still ongoing. The goal of this review is to provide guidelines as to important cytokines that can be utilized for evaluating the immunotoxicity of nanomaterials and to highlight the role of those cytokines in mediating adverse reactions, which is of particular importance for the clinical development of nanopharmaceuticals and other nanotechnology-based products. Importantly, the rational design of nanomaterials of low immunotoxicity will be discussed, focusing on synthetic nanodevices, with emphasis on both the nanoparticle-forming materials and the embedded cargoes.

Iron oxide nanoparticles and induced autophagy in human monocytes

“…Cytokines, particularly proinflammatory cytokines, are useful tools in evaluating NP immunotoxicity. 33 In the present study, we detected that proinflammatory cytokines (TNFα, IL1β, or IL6) increased after Dex-SPION exposure ( Figure 6). It was possible that Dex-SPIONs induced immunotoxicity in human monocytes by accelerating the inflammation.…”

Immuno-silent polymer capsules encapsulating nanoparticles for bioimaging applications

“…Since, cytokines are the primary molecules of immune response, the evaluation of cytokine levels are used as biomarkers for understanding immune modulation by nanomaterials. 13 19,20 In our recent reports, these polymer capsules encapsulating nanoparticles were demonstrated as biocompatible at both in vitro at in vivo levels. 16,21 Since, they possess good imaging properties along with biocompatibility and efficient internalization, it is essential to study their immune response.…”

In vitro assays for hazard identification of nanoparticles

“…NP-induced macrophage cell death may decrease the innate immune response. NPs have been shown to induce infl ammatory responses, like induction of proinfl ammatory cytokines and oxidative stress responses, in diff erent mammalian cell lines which may point at possible immunotoxicity (Nel et al 2006, Elsabahy and Wooley 2013, Watson et al 2014. NPs can interact with various components of the immune system and either enhance or inhibit its function (Elsabahy and Wooley 2013).…”

“…Intestinal and colonic macrophages represent the largest population of mononuclear phagocytes in the body. Gut macrophages are part of the fi rst-line defence mechanisms, playing a major role in the innate immune response (Ma et al 2003, Smith et al 2011, Elsabahy and Wooley 2013. NP-induced macrophage cell death may decrease the innate immune response.…”

“…Existing information on potential adverse health eff ects is mainly based on animal experiments, although in vitro studies with cell lines have recently added to the insight in potential hazards of NPs. NPs have been shown, for example, to induce cytotoxic, genotoxic, infl ammatory and oxidative stress responses in diff erent mammalian cell lines (Nel et al 2006, Elsabahy et al 2013, Watson et al 2014). …”