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.
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)
Geiger
T
T
Research Department, Pharmaceuticals Division, Ciba-Geigy Ltd., Basel, Switzerland.
Towbin
H
H
Cosenti-Vargas
A
A
Zingel
O
O
Arnold
J
J
Rordorf
C
C
Glatt
M
M
Vosbeck
K
K
D000210:Acute-Phase Reaction / Q000209:etiology / Q000517:prevention & control; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001172:Arthritis, Rheumatoid / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D001323:Autoantibodies / Q000096:biosynthesis; D003094:Collagen / Q000276:immunology*; D004195:Disease Models, Animal; D007375:Interleukin-1 / Q000037:antagonists & inhibitors* / Q000276:immunology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D009500:Neutralization Tests; D000683:Serum Amyloid P-Component / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D007375:Interleukin-1; D000683:Serum Amyloid P-Component; D003094:Collagen