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

Engineered nanomaterials (ENMs) to which humans are exposed intentionally as nanomedicines or unintentionally as invaders, may elicit unforeseen immune reactions. An uncontrollable ENM‐induced immune response poses a potential danger to the human body. During an immunological reaction, interleukin (IL)‐1 family cytokines, which play key roles under both physiological and pathological conditions, can be secreted by various types of cells into the surrounding environment to induce a series of defensive reactions. However, the crucial roles played by IL‐1 family cytokines in ENM‐induced immunological responses have not attracted enough attention from researchers to date. In this review, ENM‐mediated inflammatory responses and immunotoxicity are discussed, with the main focus directed to IL‐1 family cytokines, including IL‐1α, IL‐1β, IL‐1Ra, IL‐18, IL‐33, IL‐36, IL‐37, and IL‐38. The potential molecular mechanisms of IL‐1 family cytokine activity triggered by ENMs, particularly the activation of IL‐1α, IL‐1β, IL‐18, and IL‐33, are also reviewed. The understanding of IL‐1 family cytokines on nanoimmunosafety provides a fundamental basis for designing safe ENMs that can potentially be used for nanomedicine. This article is categorized under: Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials Nanoparticles with different physicochemical properties, including various sizes, shapes, surface charges, and modifications, can lead to inflammatory responses and subsequent IL‐1 cytokine secretion, which is a normal physiological response by the human immune system. However, the uncontrolled release of cytokines, persistent activation of inflammasomes, and persistent suppression of the immune system cause immunotoxicity in humans.