title: Synergistic protection against cartilage destruction by low dose prednisolone and interleukin-10 in established murine collagen arthritis.
abstract: 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.
  
  
  CONCLUSIONS
  This study demonstrates synergistic effects of combined treatment with prednisolone and IL-10 on suppressing disease activity of CIA as well as reducing cartilage.
authors.affiliation: Department of Rheumatology, University Hospital Nijmegen, The Netherlands. l.joosten@reuma.azn.nl
authors.forename: L A
authors.initials: LA
authors.lastname: Joosten
authors.forename: M M
authors.initials: MM
authors.lastname: Helsen
authors.forename: T
authors.initials: T
authors.lastname: Saxne
authors.forename: D
authors.initials: D
authors.lastname: Heinegård
authors.forename: L B
authors.initials: LB
authors.lastname: van de Putte
authors.forename: W B
authors.initials: WB
authors.lastname: van den Berg
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002358:Cartilage, Articular / Q000378:metabolism / Q000473:pathology*; D002417:Cattle; D003094:Collagen; D016207:Cytokines / Q000096:biosynthesis; D004357:Drug Synergism; D004797:Enzyme-Linked Immunosorbent Assay; D016326:Extracellular Matrix Proteins / Q000097:blood; D016753:Interleukin-10 / Q000008:administration & dosage / Q000096:biosynthesis / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D011239:Prednisolone / Q000008:administration & dosage / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013582:Synovial Fluid / Q000187:drug effects / Q000378:metabolism