The two 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 approximately 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.
Sims
J E
JE
Immunex Research and Development Corporation, Seattle, Washington 98101.
Giri
J G
JG
Dower
S K
SK
D000818:Animals; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology; D017472:Receptors, Interleukin-1 / Q000737:chemistry / Q000502:physiology*; D011994:Recombinant Proteins; D012995:Solubility
D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins