IL-33 belongs to the IL-1 family and is closely related in structure to IL-18 and IL-1b. IL-33, IL-1b, and IL-18 are synthesized as biologically inactive precursor 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-1b. In addition, IL-33 is a nuclear factor (NF-HEV) abundantly expressed in high endothelial venules from lymphoid organs that associates with chromatin and exhibits transcriptional regulatory properties.