BIOLOGIC BASIS FOR INTERLEUKIN-1 IN DISEASE

To understand the role of the proinflammatory cytokine interleukin-1 ( IL-1) in disease, investigators have studied how production of the dif ferent members of the IL-1 family is controlled, the various biologic activities of IL-l, the distinct and various functions of the IL-1 rec eptor (IL-1R) family, and the complexity of intracellular signaling. M ice deficient in IL-1 beta, IL-1 beta converting enzyme, and IL-1R typ e I have also been studied. Humans have been injected with IL-1 (eithe r IL-1 alpha or IL-1 beta) for enhancing bone marrow recovery and for cancer treatment. The IL-1-specific receptor antagonist (IL-1Ra) has a lso been tested in clinical trials. The topics discussed in this revie w include production and activities of IL-1 and IL-1Ra molecules, the effects of IL-1 on gene expression, functions of cell-bound and solubl e IL-1 receptors, the importance of the IL-1R accessory protein, newly discovered signal transduction pathways, naturally occurring cytokine s limiting IL-1 production or activity, the effects of blocking cycloo xygenase and nitric oxide, and the outcomes of IL-1 and IL-1Ra in huma n trials. Special attention is paid to IL-1 beta converting enzyme and programmed cell death. The roles of IL-1 in hematopoiesis, leukemia, atherosclerosis, and growth of solid tumors are also discussed. This i s a lengthy review, with 586 citations chosen to illustrate specific a reas of interest rather than a compendium of references. At the end of each section, a short commentary summarizes what the author considers established or controversial topics linking the biology of IL-1 to me chanisms of disease. (C) 1996 by The American Society of Hematology.