IL-1 receptor antagonist, IL-1RA, was initially purified from medium conditioned by human monocytes. IL-1RA belongs to the IL-1 family, which includes 11 members: IL-1α, IL-1β, IL-18, IL-33, and IL-F5 to IL-1F10. Although all members are secreted proteins, IL-RA is the only one that possesses a signal peptide, and it is secreted via the endoplasmic reticulum and Golgi apparatus. In addition to the glycosylated secreted IL-1RA, an intracellular unglycosylated isoform has been described. The two forms of IL-1RA are encoded by a single gene, generated by alternative usage of the first two exons, and their expression is regulated by two promoters. IL-1RA binds tightly to IL-1R1, blocks the binding of IL-1α and IL-1β to the receptor, inhibits the recruitment of IL-1RAP (a receptor accessory protein), and thus the signal transduction induced by IL-1α and IL-1β. IL-1RA also binds to the non-signaling/decoy receptor IL-1RII. IL-1RA exhibits potent anti-inflammatory properties in vivo and can mediate protective effects against inflammatory diseases. IL-1RA has been used in controlled clinical trials for the treatment of rheumatoid arthritis (RA). It has been reported that it reduces clinical signs and symptoms associated with the disease. IL-1RA (Kineret?, Anakinra) has also been used in the treatment of type 2 diabetes and RA.