INTERLEUKIN-1 RECEPTOR ANTAGONIST

This chapter discusses the historical background of interleukin-1 (IL-1) inhibitors and the experimental work that led to the initial identification of the molecule known as IL-1ra, which is the first described naturally occurring receptor antagonist of any cytokine or hormone-like molecule. The purification, cloning, and expression of IL-1ra, the characterization of IL-1ra protein and gene structures, and the regulation of production of IL-1ra are discussed. The multiple reports on the in vitro and in vivo effects of IL-1ra are described, including early results from studies in human diseases. Some speculations are offered on the possible biological relevance of different structural variants of IL-1ra. IL-1 was first identified as a macrophage-derived lymphocyte-activating factor (LAF) in the early 1970s. IL-1 is a 17-kDa glycoprotein that is produced primarily by monocytes and macrophages, but may be synthesized by a variety of cells in multiple organs. IL-1 has been implicated as a mediator of tissue destruction in many human diseases, including rheumatoid arthritis. The chapter discusses the widespread presence of IL-1 in different organs, its production by a variety of cells, and its hypothesized proinflammatory role in human diseases. © 1993, Academic Press Inc.