The effect of recombinant human interleukin 1 receptor antagonist on the induction phase of antigen induced arthritis in the rabbit.
OBJECTIVE
To determine if systemic administration of human interleukin 1 receptor antagonist (IL-1ra) to rabbits during the induction phase of antigen induced arthritis (AIA) could block inflammation and cartilage proteoglycan loss.


METHODS
Recombinant human IL-1ra was administered every 6 h to rabbits beginning 1 h before induction of arthritis. Joint swelling was monitored for 72 h and then animals were killed 6 h after the last dose of IL-1ra. Leukocyte accumulation in the joint space and synovial lining was determined and the proteoglycan content and capacity for synthesis was assessed in the articular cartilage of the control and arthritic joints.


RESULTS
Administration of IL-1ra had no detectable effect on the induction of arthritis. Swelling proceeded with a similar time course to untreated AIA animals and at 3 days the cellular infiltrate into synovial fluid (SF) was similarly high, the proteoglycan content of SF was also high and cartilage proteoglycan content was depleted. The biosynthesis of proteoglycan in cartilage was also similarly inhibited. No changes were detected in the cartilage and synovium or SF of the contralateral joints of animals receiving IL-1ra.


CONCLUSIONS
IL-1ra given at a dose shown to block synovitis and proteoglycan loss induced by a bolus injection of recombinant IL-1 in rabbits was unable to inhibit the induction of AIA. Our results suggest that the action of IL-1 is not the major factor responsible for the induction of arthritis in this animal model of inflammatory joint disease.
Lewthwaite
J
J
Mathilda and Terence Kennedy Institute of Rheumatology, London, UK.
Blake
S M
SM
Hardingham
T E
TE
Warden
P J
PJ
Henderson
B
B
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D000941:Antigens / Q000633:toxicity*; D001168:Arthritis / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D002358:Cartilage, Articular / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D006965:Hyperplasia; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000502:physiology*; D010047:Ovalbumin / Q000633:toxicity; D011509:Proteoglycans / Q000378:metabolism; D011817:Rabbits; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012795:Sialoglycoproteins / Q000627:therapeutic use*; D013583:Synovial Membrane / Q000473:pathology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000941:Antigens; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D011509:Proteoglycans; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins; D012795:Sialoglycoproteins; D010047:Ovalbumin