INTERLEUKIN-1 SIGNALING OCCURS EXCLUSIVELY VIA THE TYPE-I RECEPTOR

Two receptors for the proinflammatory cytokine interleukin 1 (IL-1) ha ve been cloned and characterized biochemically. While it has been well established that the type I (80-kDa) IL-1 receptor can mediate respon ses to IL-1, the function of the type II(60-kDa) IL-1 receptor has bee n unknown. In this manuscript we describe experiments designed to ask whether the type II receptor is capable of delivering a biological sig nal. We have examined two types of experimental situation: responses t o IL-1 in cells which express predominantly the type II receptor, and responses to IL-1 which have been suggested previously in the literatu re to be mediated by type II receptors. In both situations we find tha t the responses instead are mediated via type I receptors. A blocking antibody against the type II receptor never inhibits, and in fact some times enhances, the responses. We conclude that a very small number of type I receptors is sufficient to mediate all of the actions of IL-1 which we have examined here and that the function of the type II recep tor may not be to transduce signals.