Chapter 21. Interleukin-1 as a Therapeutic Target

Abstract

Publisher Summary Cytokines are intercellular polypeptide messengers that regulate cell function. Among the dozens of cytokines that are now recognized, the interleukin-1 (IL-1) family has been the most intensively studied and characterized. The IL-1 family consists of two agonists, IL-1α and IL-1 β, and a structurally related antagonist, IL-1 ra. Unless specified otherwise, the term “IL-1” refers to IL-lα and IL-1β. Comprehensive reviews have been recently published of cytokines (l), IL-1 structure, IL-1 receptors, biological activities of IL-1, IL-1 signal transduction, the role of IL-1 in disease, I L-lra structure and function, and the modulation of IL-1 in disease. Some of the pertinent points will be briefly discussed in the chapter as a background for a discussion of the recent history of IL-1, as a therapeutic target. Volume 25 of the series contains a review through 1989 of the status of pharmacological modulation of IL-1. Volume 27 contains a brief overview of the status, through 1992, of the pharmacological modulation of many cytokines, including IL-1. Studies with the specific IL-1 antagonist, IL-1ra, in vivo have strengthened the evidence that IL-1 plays a significant role in the pathogenesis of inflammatory diseases. Of the many possible points of therapeutic intervention, with IL-1 as the target, most of the medicinal chemistry activities have focused on IL-1 production inhibitors.