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

Objectives. To investigate the effects of soluble interleukin-1 (IL-1) type II receptor (sIL-1RII) on a number of clinical, biochemical and histologic al parameters in rabbit antigen-induced arthritis. Methods. Arthritis was induced by intra-articular injection of methylated b ovine 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. A nimals received vehicle (saline 500 mu l + 5 mu l/h), low-dose sIL-1RII (13 .4 mu g + 1.34 mu g/h) or high-dose sIL-1RII (40.2 mu g + 4.02 mu g/h). Results. Marked, dose-related inhibition of joint diameter, plasma prostagl andin E-2 (PGE(2)), and synovial fluid IL-1 alpha and IL-1 beta concentrati ons were seen after administration of sIL-1RII. However, synovial fluid PGE (2) concentrations and synovial fluid cell counts were not affected. A sign ificant inhibitory effect was also seen histologically on soft-tissue swell ing 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 a s an excellent animal model with respect to evaluating anti-cytokine therap ies for rheumatoid arthritis.