2 INTERLEUKIN-1 RECEPTORS PLAY DIFFERENT ROLES IN IL-1 ACTIONS

The proinflammatory cytokine interleukin-1 binds to two cell-surface receptors. The type I receptor, an 80-kDa protein with a cytoplasmic domain of approximate to 215 amino acids, mediates the biological effects of IL-1. The type II receptor, a 60-kDa protein with 29 cytoplasmic amino acids, binds IL-1 and thereby prevents it from binding to the type I receptor but does not deliver a biological signal. Thus, the type II receptor acts as a negative regulator of IL-1 actions. It can do so either as a membrane-bound molecule or subsequent to shedding from the cell surface to generate a so-called ''soluble'' receptor. Both the naturally produced soluble type II receptor and the recombinantly generated soluble type I receptor are effective inhibitors of IL-1 action. The soluble type I receptor has shown efficacy in some preclinical models of inflammatory diseases, as well as in an initial clinical trial in a setting of cutaneous allergy. (C) 1994 Academic Press, Inc.