Interleukin-33: A multifunctional alarmin that promotes both health and disease

Abstract

Interleukin-33 (IL-33) is a member of the IL-1 family of cytokines. IL-33 is present in the cell nucleus and is released into extracellular spaces, where it acts as an alarmin by binding to the receptor ST2. The receptor ST2 is widely expressed in the human body, and IL-33 exerts a wide range of biological activities depending on the target cells and cellular context. IL-33 is essential for host protection from helminth infections by promoting type 2 immune responses; IL-33 thus has an adverse effect on allergic inflammation. Furthermore, it is becoming clear that in addition to type 2 immunity-mediated diseases, IL-33 is involved in a wide variety of human diseases. IL-33 may be a predisposing factor for some inflammatory diseases, such as rheumatoid arthritis and inflammatory bowel disease, in which type 2 immunity is not involved. By contrast, IL-33 also has cardioprotective and neuroprotective properties in such conditions as ischemic heart disease, atherosclerosis, Alzheimer’s disease, and multiple sclerosis. Therefore, thorough understanding of IL-33 is essential for achieving full therapeutic application of this molecule.