Effects of soluble interleukin-1 type II receptor on rabbit antigen-induced arthritis: Clinical, biochemical and histological assessment

Abstract

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 μl + 5 μl/h), low-dose sIL-1RII (13.4 μg + 1.34 μg/h) or high-dose sIL-1RII (40.2 μg + 4.02 μg/h). Results. Marked, dose-related inhibition of joint diameter, plasma prostaglandin E2 (PGE2), and synovial fluid IL-1α and IL-1β 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.