Evidence for the biological modulation of IL-1 activity: the role of IL-1Ra

Clin Exp Rheumatol. Sep-Oct 2002;20(5 Suppl 27):S14-20.

Abstract

Interleukin-1 (IL-1) and tumor necrosis factor (TNFalpha) are key mediators of inflammation and are produced by monocyte-macrophages (Mphi) following the activation of soluble factors and contact with stimulated Th1 lymphocytes. The contact between lymphocytes and Mphi is regulated by ligand and counterligands (i.e. beta2-integrins, CD40-CD40L, CD69) and plasma lipoproteins (i.e. HDL-associated Apo-AI). IL-1 and TNFalpha are potent inducers of matrix metalloproteinases (MMPs), eicosanoids, nitric oxide oxydase (iNOS), receptor activator of NF-kappaB ligand (RANKL), products involved in the destruction of the extracellular matrix, the cartilage and in bone resorption. IL-1--particularly important at the local level--is more potent than TNF in stimulating MMPs and specifically in impeding cartilage repair. However, IL-1 and TNFalpha strongly synergize in multiple biological functions. Blockade of IL-1 by IL-1 receptor antagonist (IL-1Ra, sIL-1RII) in combination with the soluble IL-1 accessory protein (IL-1R AcP) result in a long-term beneficial effect in chronic inflammatory diseases. The association with anti-TNF therapy may also represent a logical approach, considering the number of patients that do not respond to either compound alone. An altogether new challenge would be to accomplish the blockade at a more proximal level (i.e. lymphocyte/Mphi interaction).

Publication types

  • Review

MeSH terms

  • Animals
  • Antigenic Modulation / immunology*
  • Arthritis, Rheumatoid / immunology*
  • Arthritis, Rheumatoid / physiopathology
  • Cell Communication / immunology
  • Humans
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1 / immunology*
  • Mice
  • Models, Animal
  • Rats
  • Sialoglycoproteins / antagonists & inhibitors
  • Sialoglycoproteins / immunology*
  • Tumor Necrosis Factor-alpha / immunology*

Substances

  • IL1RN protein, human
  • Il1rn protein, mouse
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1
  • Sialoglycoproteins
  • Tumor Necrosis Factor-alpha