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

First Author  Joosten LA Year  1999
Journal  Inflamm Res Volume  48
Issue  1 Pages  48-55
PubMed ID  9987683 Mgi Jnum  J:55993
Mgi Id  MGI:1339858 Doi  10.1007/s000110050396
Citation  Joosten LA, et al. (1999) Synergistic protection against cartilage destruction by low dose prednisolone and interleukin-10 in established murine collagen arthritis. Inflamm Res 48(1):48-55
abstractText  OBJECTIVE: To investigate potential synergy of low dosages glucocorticosteroids (GC's) and interleukin-10 (IL-10), using established murine collagen-induced arthritis (CIA) as a model. METHODS: DBA-1J/BOM mice were immunized with bovine type II collagen and boosted 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 micrograms/day) 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 1 and 5 mg/kg prednisolone, while a dose of 0.05 mg/kg prednisolone was ineffective. Treatment of CIA with 5 micrograms/day IL-10 resulted in a mild, but significant suppression. Synergistic effects were seen with the combination of low dose prednisolone and IL-10 (0.05 mg/kg, 1 microgram/day). Both arthritis score and joint pathology were significantly reduced. Moreover, COMP levels were significantly decreased after IL-10/prednisolone treatment, confirming decreased cartilage 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 mRNA levels for IL-10 and IL-1Ra were upregulated by combined treatment. CONCLUSION: This study demonstrates synergistic effects of combined treatment with prednisolone and IL-10 on suppressing disease activity of CIA as well as reducing cartilage.
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