IL-33 belongs to the IL-1 family and is closely related in structure to IL-18 and IL-1beta. IL-33, IL-1beta, and IL-18 are synthesized as biologically inactive precursors and are cleaved by the enzyme caspase-1 to be secreted as active mature forms. IL-33 stimulates target cells by binding to the IL-1R/TLR superfamily member ST2 and, subsequently, activates NF-kappaB and MAPK pathways via identical signalling events to those observed for IL-1beta. In addition, IL-33 is a nuclear factor (NF-HEV) abundantly expressed in high endothelial venules from lymphoid organs that associate with chromatin and exhibit transcriptional regulatory properties.