Inhibition of interleukin-1-induced synovitis and articular cartilage proteoglycan loss in the rabbit knee by recombinant human interleukin-1 receptor antagonist.
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-1 beta 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.
Henderson
B
B
Department of Maxillofacial Surgery and Oral Medicine, Eastman Dental Hospital, England.
Thompson
R C
RC
Hardingham
T
T
Lewthwaite
J
J
D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D005260:Female; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000633:toxicity*; D009504:Neutrophils / Q000502:physiology*; D011506:Proteins / Q000494:pharmacology*; D011509:Proteoglycans / Q000378:metabolism*; D011817:Rabbits; D011994:Recombinant Proteins / Q000494:pharmacology; D012795:Sialoglycoproteins; D013582:Synovial Fluid / Q000187:drug effects / Q000502:physiology; D013585:Synovitis / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D011506:Proteins; D011509:Proteoglycans; D011994:Recombinant Proteins; D012795:Sialoglycoproteins