Soluble interleukin-1 receptor — reverse signaling in innate immunoregulation

Interleukin-1 (IL-1) is one of the most important proinflammatory cytokines, regulating immunological and inflammatory processes. It induces a very efficient and self-amplifying cytokine-network. The action of IL-1 must, therefore, be under tight control. Soluble IL-1 receptor was thought to be an efficient negative regulator of the IL-1 signaling system. However, recent studies in vitro and in vivo demonstrate that soluble IL-1 receptor can act as an agonist as well, inducing intracellular signaling events. This feature of soluble IL-1 receptor adds a new level of complexity to our understanding of ligand-receptor cross-talk and cell-to-cell communication.