THE INTERLEUKIN-1 FAMILY - 10 YEARS OF DISCOVERY

Ten years ago the cloning of two interleukin-l molecules (IL-1 alpha a nd IL-1 beta) resolved the question of whether a single polypeptide co uld evoke a wide variety of biological effects. During the past decade , the biology of IL-1 has greatly expanded our understanding of how th e host responds to external challenges, such as injury and infection, as well as its role in several diseases. We learned of the remarkable potency of IL-1 in the femtomolar range and of its ability to induce a response by triggering only one or two receptors per cell. Unexpected ly, the IL-1 family of genes, receptors and associated molecules have been linked to those of Drosophila, nematodes, and microorganisms and IL-1 signal transduction is similar to that observed after cellular st ress. The cloning of IL-1 opened other avenues of fundamental biologic al interest. For example, in addition to the two agonist molecules IL- 1 alpha and IL-1 beta, a third member of the IL-1 gene family is a spe cific, high affinity receptor antagonist (IL-I receptor antagonist). T hat this third member of the IL-1 family inhibits the other two is cha racteristic of the tight control over production and activity exerted on IL-1. Although IL-1 contributes to the pathogenesis of many disease s, a small amount appears to be needed to combat infection and initita te healing processes. This article highlights 10 years of discoveries on IL-1.-Dinarello, C.A. The interleukin-l family: 10 years of discove ry.