IL-33 is a newly recognized cytokine of the IL-1 cytokine family that has recently been attributed to the epithelial “alarmin” defense system. IL-33 is released by the epithelial cells in various tissues and organs, including keratinocytes, endothelial cells, and immune cells. Recent reports have suggested that IL-33 might be a critical part of the innate immunity, although its precise role is as yet poorly understood. In several organs, IL-33 appears to drive T helper type 2 (Th2) responses, suggesting roles in allergic and atopic diseases, as well as in fibrosis. IL-33 exerts its effects by activating the ST2 (suppression of tumorigenicity 2)/IL-1 aR receptor on different types of cells, including mast cells and Th2 cells. The ST2 receptor is either expressed on the cell surface or shed from these cells (soluble ST2, sST2), thereby functioning as a “decoy” receptor. After binding to its receptor, IL-33 activates NF-κB, suggesting that it regulates the outcome of diseases such as atopic dermatitis. On the other hand, several studies have reported on the inhibitory effects of sST2 in inflammatory and fibrotic diseases, suggesting that IL-33/ST2 is a unique cytokine with potential pro- and anti-inflammatory effects.
