Neutralization of interleukin-1 beta activity in vivo with a monoclonal antibody alleviates collagen-induced arthritis in DBA/1 mice and prevents the associated acute-phase response

Clin Exp Rheumatol. Sep-Oct 1993;11(5):515-22.

Abstract

Interleukin-1 (IL-1) has been implicated in the development and progression of a variety of acute and chronic inflammatory diseases. Due to its pro-inflammatory and tissue-degrading activities, IL-1 is regarded as a major mediator of chronic inflammatory joint diseases, including rheumatoid arthritis in man, adjuvant arthritis in rats and collagen-induced arthritis in mice. However, conclusive experimental evidence for the crucial role of IL-1 in the development of joint destruction has not been presented as yet. In the present study, we investigated the effect of a neutralizing monoclonal mouse antibody against mouse IL-1 beta (IgG1 isotype) on the development and progression of collagen-induced arthritis in DBA/1 mice. The antibody was injected intraperitoneally 3 times a week, either from day 3 or from day 21 after primary immunization, to day 60. In the positive control group an arthritis incidence of 80% was observed after 60 days. The injection of a control antibody of the same isotype did not influence the incidence of arthritis, whereas injection of anti-IL-1 beta from day 21 reduced the arthritis incidence to about 30%. Injection of anti-IL-1 beta starting at day 3 totally prevented both the development of arthritis and the associated increase of the acute phase protein serum amyloid P (SAP). Anti-collagen antibody titers, which increased significantly after immunization, were not influenced by the injection of anti-IL-1 beta antibodies, in spite of the suppressive effect on arthritis development.(ABSTRACT TRUNCATED AT 250 WORDS)

MeSH terms

  • Acute-Phase Reaction / etiology
  • Acute-Phase Reaction / prevention & control
  • Animals
  • Antibodies, Monoclonal / pharmacology*
  • Arthritis, Rheumatoid / etiology
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / prevention & control*
  • Autoantibodies / biosynthesis
  • Collagen / immunology*
  • Disease Models, Animal
  • Interleukin-1 / antagonists & inhibitors*
  • Interleukin-1 / immunology
  • Male
  • Mice
  • Mice, Inbred DBA
  • Neutralization Tests
  • Serum Amyloid P-Component / metabolism
  • T-Lymphocytes / immunology

Substances

  • Antibodies, Monoclonal
  • Autoantibodies
  • Interleukin-1
  • Serum Amyloid P-Component
  • Collagen