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 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.
Dinarello
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Department of Medicine, Tufts University, Boston, MA USA.
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D017209:Apoptosis; D017173:Caenorhabditis elegans / Q000201:enzymology / Q000235:genetics; D020170:Caspase 1; D002986:Clinical Trials as Topic; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use; D003546:Cysteine Endopeptidases / Q000502:physiology; D016207:Cytokines / Q000502:physiology / Q000627:therapeutic use; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D015801:Helminth Proteins / Q000235:genetics / Q000502:physiology; D006410:Hematopoiesis; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000145:classification / Q000172:deficiency / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D051379:Mice; D008875:Middle Aged; D009369:Neoplasms / Q000503:physiopathology; D051381:Rats; D017472:Receptors, Interleukin-1 / Q000145:classification / Q000187:drug effects / Q000502:physiology; D012795:Sialoglycoproteins / Q000235:genetics / Q000502:physiology / Q000627:therapeutic use; D015398:Signal Transduction / Q000502:physiology
D016861:Cyclooxygenase Inhibitors; D016207:Cytokines; D015801:Helminth Proteins; C507763:IL1RN protein, human; C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins; D003546:Cysteine Endopeptidases; D020170:Caspase 1