Synergistic protection against cartilage destruction by low dose prednisolone and interleukin-10 in established murine collagen arthritis

Objective: To investigate potential synergy of low dosages glucocorticoster oids (GC's) and interleukin-10 (IL-10), using established murine collagen-i nduced arthritis (CIA) as a model. Methods: DBA-1J/BOM mice were immunized with bovine type Il collagen and bo osted at day 21. Mice with established CIA were selected and treated for at least 7 days with either prednisolone (0.05-5 mg/kg), IL-10 (0.1-5 mu g/da y) or the combination of prednisolone/IL-10 (0.05/1 and 0.05/5). Arthritis score was monitored visually, and joint pathology was examined by histology , and serum cartilage oligomeric matrix protein (COMP) measured. Results: Amelioration of CIA was found with dosages of I and 5 mg/kg predni solone, while a dose of 0.05 mg/kg prednisolone was ineffective. Treatment of CIA with 5 mu g/day IL-10 resulted in a mild, but significant suppressio n. Synergistic effects were seen with the combination of low dose prednisol one and IL-10 (0.05 mg/kg, I mu g/day). Both arthritis score and joint path ology were significantly reduced. Moreover, COMP levels were significantly decreased after IL-10/prednisolone treatment, confirming decreased cartilag e involvement. Of great interest, treatment of CIA with prednisolone/IL-10 markedly reduced IL-1 beta and enhanced IL-10 production by synovial tissue . In addition, synovial mRNA levels for IL-1 beta were decreased, while mRN A levels for IL-10 and IL-1Ra were upregulated by combined treatment. Conclusion This study demonstrates synergistic effects of combined treatmen t with prednisolone and IL-10 on suppressing disease activity of CIA as wel l as reducing cartilage.