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 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.
Joosten
L A
LA
Department of Rheumatology, University Hospital Nijmegen, The Netherlands. l.joosten@reuma.azn.nl
Helsen
M M
MM
Saxne
T
T
Heinegård
D
D
van de Putte
L B
LB
van den Berg
W B
WB
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