The inhibitory activity of human interleukin-1 receptor antagonist is enhanced by type II interleukin-1 soluble receptor and hindered by type I interleukin-1 soluble receptor.

摘要: Interleukin-1 (IL-1) is a major proinflammatory cytokine produced by monocytes/macrophages. At the inflammatory site, IL-1 potent inducer of production prostaglandin E2 (PGE2) and metalloproteinases on fibroblast-like cells, thus triggering tissue damage. The biological activity counterbalanced two types inhibitors: receptor antagonist (IL-1Ra) which competitively binds without inducing signal transduction; soluble receptors (IL-1sR) bind diminish free concentration cytokine, hampering its binding to cell surface receptor. Since IL-1sR can also IL-1Ra, we studied simultaneous effects both inhibitors interstitial collagenase (C'ase) PGE2 human dermal fibroblasts synovial cells stimulated either alpha or beta. IL-1Ra inhibited fibroblast stimulation approximately 90%, with exception C'ase was 55%. Type I (IL-1sRI) preferentially alpha, whereas type II (IL-1sRII) mainly When used simultaneously IL-1sRI, final inhibition lower than that inhibitors. presence IL-1sRII abolished IL-1-induced demonstrating concurrently these are able abolish most response. To our knowledge, this first example each other's effects, one acts at level other ligand level, leaving unimpaired.