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Biologic basis for interleukin-1 in disease Dinarello CABlood 1996[Mar]; 87 (6): 2095-147To understand the role of the proinflammatory cytokine interleukin-1 (IL-1) in disease, investigators have studied how production of the different members of the IL-1 family is controlled, the various biologic 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-1Beta, IL-1Beta converting enzyme, and IL-1R type I have also been studied. Humans have been injected with IL-1 (either IL-1alpha or IL-1beta) for enhancing bone marrow recovery and for cancer treatment. The IL-1-specific receptor antagonist (IL-1Ra) has also been tested in clinical trials. The topics discussed in this review include production and activities of IL-1 and IL-1Ra molecules, the effects of IL-1 on gene expression, functions of cell-bound and soluble IL-1 receptors, the importance of the IL-1R accessory protein, newly discovered signal transduction pathways, naturally occurring cytokines limiting IL-1 production or activity, the effects of blocking cyclooxygenase and nitric oxide, and the outcomes of IL-1 and IL-1 Ra in human trials. Special attention is paid to IL-1beta converting enzyme and programmed cell death. The roles of IL-1 in hematopoiesis, leukemia, atherosclerosis, and growth of solid tumors are also discussed. This is a lengthy review, with 586 citations chosen to illustrate specific areas 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 mechanisms of disease.|Adult[MESH]|Aged[MESH]|Aged, 80 and over[MESH]|Animals[MESH]|Apoptosis[MESH]|Caenorhabditis elegans/enzymology/genetics[MESH]|Caspase 1[MESH]|Clinical Trials as Topic[MESH]|Cyclooxygenase Inhibitors/therapeutic use[MESH]|Cysteine Endopeptidases/physiology[MESH]|Cytokines/physiology/therapeutic use[MESH]|Female[MESH]|Gene Expression Regulation/drug effects/physiology[MESH]|Helminth Proteins/genetics/physiology[MESH]|Hematopoiesis[MESH]|Humans[MESH]|Inflammation/*physiopathology[MESH]|Interleukin 1 Receptor Antagonist Protein[MESH]|Interleukin-1/classification/deficiency/genetics/pharmacology/*physiology[MESH]|Male[MESH]|Mice[MESH]|Middle Aged[MESH]|Neoplasms/physiopathology[MESH]|Rats[MESH]|Receptors, Interleukin-1/classification/drug effects/physiology[MESH]|Sialoglycoproteins/genetics/physiology/therapeutic use[MESH]|Signal Transduction/physiology[MESH] |
