The importance of the IL-1 family of cytokines in nanoimmunosafety and nanotoxicology

“

How ENMs with various physical and chemical properties (e.g., size, shape, chemical composition, surface structure, or solubility) affect the secretion of IL-1 family cytokines has not been effectively evaluated. In general, little is known about the cellular or molecular mechanisms by which ENMs affect the secretion of IL-1 family cytokines. Although ENMs have been found to induce secondary signaling to activate inflammasome leading to IL-1β/18 secretion, the other cytokines secreted are also largely unknown. Therefore, more studies need to be conducted not only in the nanotoxicology field but also in the immune-biology field to gain a better understanding of the molecular mechanisms by which these cytokines are secreted during immune reactions. To better elaborate on the immunotoxicity induced by ENMs, we need to apprehend the crucial role played by IL-1 family cytokines in immunity and accurately evaluate the secretion of these cytokines upon ENM stimulation with both in vitro and in vivo models in future studies. For accurate assessments, ENMs need to be carefully characterized in terms of both their physicochemical properties and related bioactive contaminants, which may affect potential EMN immunotoxicity. In addition, ENMs can change protein structure, protein–protein interactions, and protein activation. Thus, they may interfere with the immunotoxicity tests and cause false negative or positive results. Furthermore, endotoxin can mask the real immunotoxicity of ENMs. Therefore, in contrast to those of traditional drugs, immunotoxicity tests of ENMs may involve more testing methods performed in parallel. To this end, computational tools can also be employed. With the development of nanotechnology and the study of nanotoxicology, quantitative structure–activity relationship (QSAR) modeling may be useful in analyzing the immunotoxicity of ENMs in the future with emphasis on IL-1 family cytokines.

”