Interleukin-1, interleukin-1 Receptors and interleukin-1 Receptor Antagonist

Int Rev Immunol. 1998;16(5-6):457-99. doi: 10.3109/08830189809043005.

Abstract

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.

Publication types

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

MeSH terms

  • Animals
  • Apoptosis
  • Caspase 1
  • Cysteine Endopeptidases / metabolism
  • Cytokines / immunology
  • Cytokines / metabolism
  • Humans
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1* / administration & dosage
  • Interleukin-1* / genetics
  • Interleukin-1* / metabolism
  • Interleukin-18
  • Mice
  • Receptors, Interleukin-1* / metabolism
  • Sialoglycoproteins* / administration & dosage
  • Sialoglycoproteins* / metabolism
  • Sialoglycoproteins* / therapeutic use
  • fas Receptor / metabolism

Substances

  • Cytokines
  • IL1RN protein, human
  • Il1rn protein, mouse
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1
  • Interleukin-18
  • Receptors, Interleukin-1
  • Sialoglycoproteins
  • fas Receptor
  • Cysteine Endopeptidases
  • Caspase 1