Interleukin 18 (IL-18) is a member of the IL-1 family of cytokines and shares numerous immunoregulatory functions with IL-12. The functional IL-18 receptor complex is composed of two subunits designated IL-18 R alpha (also termed IL-1 R5 and IL-1 Rrp) and IL-18 R beta (also termed IL-1 R7 and AcPL). Both IL-18 R alpha and IL-18 R beta belong to the IL-1 receptor superfamily. Although IL-18 R by itself binds IL-18 with low affinity and IL-18 R beta does not bind IL-18 in vitro, co-expression of IL?18 R alpha and IL?18 R beta is required for high affinity binding and IL-18 responsiveness. Human IL-18 R cDNA encodes a 541 amino acid (aa) precursor type I membrane protein with a hydrophobic signal, an extracellular domain comprised of three immunoglobulin-like domains, a transmembrane domain and a cytoplasmic region of approximately 200 aa. Human and mouse IL-18 R share 65% amino acid sequence homology. IL-18 R is widely expressed in numerous tissues including spleen, thymus, leukocyte, liver, lung, heart, small and large intestine, prostate and placenta.