INHIBITION OF INTERLEUKIN-1-INDUCED SYNOVITIS AND ARTICULAR-CARTILAGE PROTEOGLYCAN LOSS IN THE RABBIT KNEE BY RECOMBINANT HUMAN INTERLEUKIN-1 RECEPTOR ANTAGONIST

被引:105
作者
HENDERSON, B
THOMPSON, RC
HARDINGHAM, T
LEWTHWAITE, J
机构
[1] UCL EASTMAN DENT HOSP, INST DENT SURG, DEPT MAXILLOFACIAL SURG & ORAL MED, LONDON WC1X 8LD, ENGLAND
[2] SYNERGEN INC, BOULDER, CO 80301 USA
[3] KENNEDY INST, DIV BIOCHEM, LONDON W6 7DW, ENGLAND
关键词
ARTHRITIS; RABBIT; INTERLEUKIN-1; INTERLEUKIN-1 RECEPTOR ANTAGONIST;
D O I
10.1016/1043-4666(91)90023-7
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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-1β 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. © 1991.
引用
收藏
页码:246 / 249
页数:4
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