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 interleuki n 1 receptor antagonist (1L-1ra) to rabbits during the induction phase of antigen induced arthritis (AIA) could block inflammation and carti lage proteoglycan loss. Methods. Recombinant human IL-1ra was administ ered 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 s pace and synovial lining was determined and the proteoglycan content a nd capacity for synthesis was assessed in the articular cartilage of t he control and arthritic joints. Results. Administration of IL-1ra had no detectable effect on the induction of arthritis. Swelling proceede d with a similar time course to untreated AIA animals and at 3 days th e cellular infiltrate into synovial fluid (SF) was similarly high, the proteoglycan content of SF was also high and cartilage proteoglycan c ontent was depleted. The biosynthesis of proteoglycan in cartilage was also similarly inhibited. No changes were detected in the cartilage a nd synovium or SF of the contralateral joints of animals receiving IL- 1ra. Conclusion. IL-1ra given at a dose shown to block synovitis and p roteoglycan loss induced by a bolus injection of recombinant IL-1 in r abbits was unable to inhibit the induction of ALA. Our results suggest that the action of IL-1 is not the major factor responsible for the i nduction of arthritis in this animal model of inflammatory joint disea se.