Rheumatology, Vol 38, 401-406, Copyright © 1999 by British Society for Rheumatology
J Dawson, P Engelhardt, T Kastelic, D Cheneval, A MacKenzie and P Ramage
OBJECTIVES: To investigate the effects of soluble interleukin-1 (IL-1) type
II receptor (sIL-1RII) on a number of clinical, biochemical and
histological parameters in rabbit antigen-induced arthritis. METHODS:
Arthritis was induced by intra-articular injection of methylated bovine
serum albumin (mBSA) into rabbits pre-sensitized to the same antigen. An
initial i.v. bolus of sIL-1RII was administered, followed by s.c. mini-pump
dosing for 14 days, starting at the time of the arthritis induction.
Animals received vehicle (saline 500 microl + 5 microl/h), low-dose
sIL-1RII (13.4 microg + 1.34 microg/h) or high-dose sIL-1RII (40.2 microg +
4.02 microg/h). RESULTS: Marked, dose-related inhibition of joint diameter,
plasma prostaglandin E2 (PGE2), and synovial fluid IL-1alpha and IL-1beta
concentrations were seen after administration of sIL-1RII. However,
synovial fluid PGE2 concentrations and synovial fluid cell counts were not
affected. A significant inhibitory effect was also seen histologically on
soft-tissue swelling and joint damage with high-dose sIL-1RII. CONCLUSIONS:
These results demonstrate that IL- 1 plays an important role in the
pathogenesis of rabbit antigen-induced arthritis, thus confirming it as an
excellent animal model with respect to evaluating anti-cytokine therapies
for rheumatoid arthritis.
ORIGINAL PAPERS
Effects of soluble interleukin-1 type II receptor on rabbit antigen- induced arthritis: clinical, biochemical and histological assessment
Department of Arthritis and Bone Metabolism, Novartis Pharma AG, Basel, Switzerland.
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