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

Inflamm Res. 1999 Jan;48(1):48-55. doi: 10.1007/s000110050396.

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.

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.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / pharmacology*
  • Arthritis, Experimental / metabolism
  • Arthritis, Experimental / pathology
  • Arthritis, Experimental / prevention & control*
  • Cartilage, Articular / metabolism
  • Cartilage, Articular / pathology*
  • Cattle
  • Collagen
  • Cytokines / biosynthesis
  • Drug Synergism
  • Enzyme-Linked Immunosorbent Assay
  • Extracellular Matrix Proteins / blood
  • Interleukin-10 / administration & dosage
  • Interleukin-10 / biosynthesis
  • Interleukin-10 / pharmacology*
  • Male
  • Mice
  • Mice, Inbred DBA
  • Prednisolone / administration & dosage
  • Prednisolone / pharmacology*
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / isolation & purification
  • Reverse Transcriptase Polymerase Chain Reaction
  • Synovial Fluid / drug effects
  • Synovial Fluid / metabolism

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Extracellular Matrix Proteins
  • RNA, Messenger
  • Interleukin-10
  • Collagen
  • Prednisolone