Biologic basis for interleukin-1 in disease

Blood. 1996 Mar 15;87(6):2095-147.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Apoptosis
  • Caenorhabditis elegans / enzymology
  • Caenorhabditis elegans / genetics
  • Caspase 1
  • Clinical Trials as Topic
  • Cyclooxygenase Inhibitors / therapeutic use
  • Cysteine Endopeptidases / physiology
  • Cytokines / physiology
  • Cytokines / therapeutic use
  • Female
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology
  • Helminth Proteins / genetics
  • Helminth Proteins / physiology
  • Hematopoiesis
  • Humans
  • Inflammation / physiopathology*
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1 / classification
  • Interleukin-1 / deficiency
  • Interleukin-1 / genetics
  • Interleukin-1 / pharmacology
  • Interleukin-1 / physiology*
  • Male
  • Mice
  • Middle Aged
  • Neoplasms / physiopathology
  • Rats
  • Receptors, Interleukin-1 / classification
  • Receptors, Interleukin-1 / drug effects
  • Receptors, Interleukin-1 / physiology
  • Sialoglycoproteins / genetics
  • Sialoglycoproteins / physiology
  • Sialoglycoproteins / therapeutic use
  • Signal Transduction / physiology

Substances

  • Cyclooxygenase Inhibitors
  • Cytokines
  • Helminth Proteins
  • IL1RN protein, human
  • Il1rn protein, mouse
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1
  • Receptors, Interleukin-1
  • Sialoglycoproteins
  • Cysteine Endopeptidases
  • Caspase 1