Three structurally related ligands for IL-1Rs have been described. These include two agonists, IL-1? and IL-1?, and a specific receptor antagonist, IL-1R?. Two distinct receptors designated IL-1RI and IL-1RII have been identified, each of which belong to the Ig superfamily. The preponderance of evidence suggests IL-1RI to be the functional IL-1 receptor. Binding of IL-1 to its cognate receptor results in the activation of the NF?B signaling pathway. The IL-1-dependent kinase termed IRAK (for IL-1 receptor-associated kinase) co-immunoprecipitates with activated IL-1RI and has been implicated as an upstream mediator of NF?B activation. Additional support for this assertion comes from the fact that a related Drosophila protein, Pelle, is a known upstream activator of Dorsal, the Drosophila homolog of NF?B.