ABSTRACT
The discovery of IL-1 receptor antagonist As early as 1983/1984, before the cloning of IL-1, Dayer and coworkers suspected the presence of a potential inhibitor to IL-1. Indeed, pursuing the goal of isolating large amounts of IL-1 using the bioassay of stimulation of collagenase and prostaglandin on synovial cells, their attention was drawn to diseases associated with large amounts of monocytes, i.e. monocytic leukemia, or diseases associated with a high temperature or chronic debilitating diseases such as RA and juvenile rheumatoid arthritis. To their surprise, since the screening for IL-1 was only possible by bioassay (no immunoassays were available at that time), they failed to detect IL-1 biological activities in serum or urine of seriously ill patients suffering from the above diseases.This prompted their hypothesis that IL-1 might be masked by inhibitory molecules, and after biochemical purification a factor of approximately 17 kDa was isolated from the urine of patients with monocytic leukemia.This factor specifically blocked the biological activities of IL-1, without affecting those of TNF-_.This was the first identification of IL-1 receptor antagonist in vivo.
