Interleukin 1 receptor antagonist (IL-1ra) is a naturally occurring anti-inflammatory protein secreted by macrophages, monocytes, neutrophils, fibroblasts, and epithelial cells. IL-1ra, a member of the IL-1 family, binds to IL-1 receptors in competition with IL-1 without inducing any cellular responses. It inhibits the activity of IL-1α and IL-1β by competitively blocking their type I and type II receptors. Furthermore, IL-1ra inhibits the secretion of IL-2 and the expression of IL-2 receptors. It has been shown that IL-1ra is capable of blocking the inflammatory responses induced by IL-1 both
in vitro and
in vivo. The non-glycosylated recombinant human IL-1ra expressed in
E. coli blocks binding of IL-1 as well as the glycosylated natural form. The protein shows 26% amino acid homology to IL-1β and 19% homology to IL-1α. It has been shown that excess amounts of IL-1ra are necessary in
in vitro systems to show significant inhibition of IL-1 induced responses.