Interleukin-33 (IL-33) is a recently identified member of the IL-1 family of cytokines whose other members include IL-1alpha/beta, IL-1Ra and IL-18. Its receptor has been shown to be ST2, an IL-1 receptor family member that also acts as a negative regulator of TLR-IL-1R signaling and IL-1R accessory protein (IL-1RAcP). Receptor binding of IL-33 activates NF-kappaB and MAP kinases and induces the expression of TH2-associated cytokines such as IL-4, IL-5 and IL-6. Prolonged IL-33 treatment of mice led to the development of eosinophilia, splenomegaly, and severe pathological changes in mucosal organs such as lungs, esophagus and small intestine. Recent experiments have shown that IL-33 can also co-localize with heterochromatin and possesses transcriptional repressor activities, indicating that IL-33 may function as both a proinflammatory cytokine and an intracellular nuclear factor with transcriptional regulatory properties. Despite its predicted molecular weight, IL-33 will often run at higher molecular weight in SDS-PAGE.

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