Interleukin-1, interleukin-1 receptors and interleukin-1 receptor antagonist.
IL-1 (IL-1 alpha or IL-1 beta) 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-1 beta, 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-1 beta, IL-1 beta converting enzyme (ICE) and IL-1R type I have also been studied. Humans have been injected with IL-1 (either 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 also been tested in clinical trials.
Dinarello
C A
CA
Department of Medicine, University of Colorado Health Science Center, Denver 80262, USA.
D000818:Animals; D017209:Apoptosis; D020170:Caspase 1; D003546:Cysteine Endopeptidases / Q000378:metabolism; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism; D020382:Interleukin-18; D051379:Mice; D017472:Receptors, Interleukin-1 / Q000378:metabolism; D012795:Sialoglycoproteins / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use; D019014:fas Receptor / Q000378:metabolism
D016207:Cytokines; C507763:IL1RN protein, human; C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D020382:Interleukin-18; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins; D019014:fas Receptor; D003546:Cysteine Endopeptidases; D020170:Caspase 1