IL-33, encoded by IL-33 gene located on the Chr.9 in humans, is a 30 kDa proinflammatory protein belonging to the IL-1 superfamily and it shares less than 20 % a.a. sequence identity with other members. IL-33 secreted by high endothelial venules at high levels, which is found in tonsils, peyer patches and mesenteric lymph nodes, but not in placenta. It is upregulated in arterial smooth muscle, dermal fibroblasts, and keratinocytes following IL1α or IL1β stimulation. It elicits its biological effects by interacting with IL1RL1/ST2 and its stimulation recruits MYD88, IRAK1, IRAK4, and TRAF6, followed by phosphorylation of MAPK3/ERK1 and/or MAPK1/ERK2, MAPK14, and MAPK8. IL-33 mature protein has 52-58 % a.a. sequence identity with mouse and rat IL-33.