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/

Interieukin-1 (IL-1) has been implicated in the development and progre ssion of a variety of acute and chronic inflammatory disease's. Due to its pro-inflammatory and tissue-degrading activities, IL-1 is regarde d as a major mediator of chronic inflammatory joint diseases, includin g 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 h as not been presented as yet. In the present study, we investigated th e effect of a neutralizing monoclonal mouse antibody against mouse IL- 1beta (IgG1 isotype) on the development and progression of collagen-in duced arthritis in DBA/1 mice. The antibody was injected intraperitone ally 3 times a week, either from day 3 or from day 21 after primary im munization, to day 60. In the positive control group an arthritis inci dence of 80% was observed after 60 days. The injection of a control an tibody of the same isotype did not influence the incidence of arthriti s, whereas injection of anti-IL-1beta from day 21 reduced the arthriti s incidence to about 30%. Injection of anti-IL-1beta starting at day 3 totally prevented both the development of arthritis and the associate d increase of the acute phase protein serum amyloid P (SAP). Anti-coll agen antibody titers, which increased significantly after immunization , were not influenced by the injection of anti-IL-1beta antibodies, in spite of the suppressive effect on arthritis development. Joint destr uction in the arthritic animals, as measured by X-ray scoring, was sig nificantly influenced towards normalization in the animals treated wit h anti-IL-1beta antibodies. Taken together, our results present clear evidence for the involvement of IL-1beta in the development and progre ssion of collagen arthritis in mice.