Inhibition of interleukin-1-induced synovitis and articular cartilage proteoglycan loss in the rabbit knee by recombinant human interleukin-1 receptor antagonist

Cytokine. 1991 May;3(3):246-9. doi: 10.1016/1043-4666(91)90023-7.

Abstract

Intra-articular injection of interleukin-1 (IL-1) into the knee joints of rabbits produces a synovitis associated with the loss of proteoglycan from the matrix of articular cartilage. This experimental finding supports the hypothesis that IL-1 is a possible mediator of the pathology of inflammatory joint diseases and suggests that antagonism of IL-1 could offer a therapeutic approach to these diseases. It has recently been reported that culture of human monocytes on adherent IgG stimulates these cells to synthesize a specific inhibitor of IL-1 bioactivity (IL-1ra) that acts as a receptor antagonist with lymphocytes and mesenchymal cells. We have now shown that intravenous injection of IL-1ra into rabbits given an intra-articular injection of recombinant IL-1 beta not only inhibits the entry of leukocytes into the synovial lining and joint cavity but blocks the ability of IL-1 to cause loss of proteoglycan from articular cartilage. This ability of IL-1ra to inhibit IL-1-induced arthritis in the rabbit reveals that this protein has appropriate pharmacokinetic and pharmacodynamic properties and further strengthens the belief that it may be a useful therapeutic agent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cartilage, Articular / drug effects
  • Cartilage, Articular / physiology*
  • Cartilage, Articular / physiopathology
  • Female
  • Humans
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1 / toxicity*
  • Neutrophils / physiology*
  • Proteins / pharmacology*
  • Proteoglycans / metabolism*
  • Rabbits
  • Recombinant Proteins / pharmacology
  • Sialoglycoproteins*
  • Synovial Fluid / drug effects
  • Synovial Fluid / physiology
  • Synovitis / chemically induced
  • Synovitis / physiopathology
  • Synovitis / prevention & control*

Substances

  • IL1RN protein, human
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1
  • Proteins
  • Proteoglycans
  • Recombinant Proteins
  • Sialoglycoproteins