OBJECTIVE--To determine if the administration of interleukin-1 receptor antagonist (IL-1ra) to animals with established antigen induced arthritis had any beneficial effects on the synovitis and cartilage destruction. METHODS--Antigen induced arthritis was induced in New Zealand White rabbits, and after two weeks IL-1ra was administered every six hours over a 72 hour period. Animals were then killed and joint tissues examined for the degree of synovitis, synovial fibrosis, and cartilage damage. RESULTS--The response of the arthritis to the treatment was minor in terms of joint swelling, leucocyte accumulation, or cartilage proteoglycan loss. However, the synovial fibrosis was not only halted by administration of IL-1ra, but reversed. The inflamed synovial linings of IL-1ra treated animals showed a significant loss of synovial collagen content and a reappearance of the synovial fat spaces which are prominent in the normal synovial lining. CONCLUSION--This study shows that IL-1ra has potent antifibrotic activity and suggests the use of this agent for the reversal of the fibroproliferative process which is so important in the pathology of rheumatoid arthritis.
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