Interleukin-1 receptor antagonist [IL-1F3]

The pleiotropic, and ubiquitous inflammatory activities of interleukin-1 (IL-1) suggested to many investigators that natural inhibitory mechanisms or molecules must exist. IL-1 inhibitors theoretically work at the levels of synthesis, secretion, receptor, or post-receptor intracellular pathways in cells. Early studies had described IL-1 inhibitory bioactivities in human urine, and in a variety of cell supernatants. However, many of these activities turned out to be artifacts of bioassay systems or remained uncharacterized. At a symposium, in Ann Arbor, MI, two different groups first reported bioactivities known to be interleukin-1 receptor antagonist (IL-1Ra). The dialyzed and concentrated urine of a patient with acute monocytic leukemia, and fever inhibited the effects of IL-1 on induction of PGE_2, and collagenase production by cultured human dermal fibroblasts. The supernatants of human monocytes cultured on adherent immune complexes exhibited an activity inhibitory toward IL-1 stimulation of proliferation of murine thymocytes. IL-IRa is the first described naturally occurring specific receptor antagonist of any cytokine or hormone like molecule. The chapter reviews the characteristics of the IL-1Ra gene and protein isoforms, biological role in normal physiology and in disease, potential therapeutic uses of exogenous administration, and areas of current inquiry and research.