THE EFFECTS OF ORALLY-ADMINISTERED CALCIUM PENTOSAN POLYSULFATE ON INFLAMMATION AND CARTILAGE DEGRADATION PRODUCED IN RABBIT JOINTS BY INTRAARTICULAR INJECTION OF A HYALURONATE POLYLYSINE COMPLEX

Objective. To determine the antiinflammatory and cartilage-protecting activities of orally administered calcium pentosan polysulfate (CaPPS) in a rabbit model of inflammatory arthritis. Methods. A single intraarticular injection of a preformed polycation complex (PC) of poly-D-lysine and hyaluronan was used to induce joint inflammation; saline was injected into the contralateral joint as a control. Animals were killed 1, 4, 7, or 10 days post-PC injection. CaPPS, at 5 mg/kg, 10 mg/kg, or 75 mg/kg, was given every 48 hours commencing 7 days prior to PC injection. Serum interleukin-6 (IL-6), synovial fluid (SF) prostaglandin E(2), cell numbers, and cartilage proteoglycan (PG) content, composition, and biosynthesis were determined for PC- and saline-injected joints. Results. In PC-injected, non-drug-treated animals, serum IL-6 activity, SF leukocyte numbers, and prostaglandin E(2) levels were elevated, while cartilage PG content and biosynthesis were reduced. CaPPS at 10 mg/kg, but not at 5 mg/kg, decreased serum IL-6 levels but maintained cartilage PG concentration and biosynthesis. However, SF leukocyte counts and prostaglandin E(2) levels (except on day 1) were not reduced. Conclusion. The ability of CaPPS to attenuate serum IL-6 levels and preserve cartilage PGs in inflamed rabbit joints suggests that this substance could be of value as an effective orally administered chondroprotective, antiarthritic drug.