Interleukin-1, Interleukin-1 Receptors and Interleukin-1 Receptor Antagonist

Abstract

IL-1 (IL-1α or IL-1β) is the prototypic “multifunctional” cytokine. Unlike the lymphocyte and colony stimulating growth factors, IL-1 affects nearly every cell type, and often in concert with other cytokines or small mediator molecules. Although some lymphocyte and colony stimulating growth factors may be therapeutically useful, IL-1 is a highly inflammatory cytokine and the margin between clinical benefit and unacceptable toxicity in humans is exceedingly narrow. In contrast, agents that reduce the production and/or activity of IL-1 are likely to have an impact on clinical medicine. In support of this concept, there is growing evidence that the production and activity of IL-1, particularly IL-1β, are tightly regulated events as if nature has placed specific “road blocks” to reduce the response to IL-1 during disease. In addition to controlling gene expression, synthesis and secretion, this regulation extends to surface receptors, soluble receptors and a receptor antagonist. Investigators have studied how production of the different members of the IL-1 family is controlled, the various biological activities of IL-1, the distinct and various functions of the IL-1 receptor (IL-1R) family and the complexity of intracellular signaling. Mice deficient in IL-1β, IL-1β converting enzyme (ICE) and IL-1R type I have also been studied. Humans have been injected with IL-1 (either IL-1α or IL-1β) for enhancing bone marrow recovery and for cancer treatment. The IL-1 specific receptor antagonist (IL-IRa) has also been tested in clinical trials.

Key Words:

• Cytokines
• IL-1β converting enzyme
• Inflammation
• Host defense