Cyclosporin A prevents the histologic damage of antigen arthritis without inducing fibrosis

• Published in: Arthritis and rheumatism 2000-02, Vol.43 (2), p.311-319
• Main Authors: Benito, Maria J., Sánchez‐Pernaute, Olga, José López‐Armada, Maria, Hernández, Purificación, Palacios, Itziar, Egido, Jesús, Herrero‐Beaumont, Gabriel
• Format: Article
• Language: English
• Subjects: Animals; Arthritis, Experimental - pathology; Arthritis, Experimental - prevention & control; Biological and medical sciences; Cells, Cultured; Collagen - metabolism; Cyclosporine - blood; Cyclosporine - pharmacology; Cyclosporine - therapeutic use; Disease Models, Animal; Diseases of the osteoarticular system; Fibrosis; Gene Expression; Inflammatory joint diseases; Joints - pathology; Macrophages; Medical sciences; Platelet-Derived Growth Factor - genetics; Rabbits; RNA, Messenger - metabolism; Staining and Labeling; Synovial Membrane - chemistry; Synovial Membrane - cytology; Synovial Membrane - pathology; Transforming Growth Factor beta - biosynthesis; Transforming Growth Factor beta - genetics; Transforming Growth Factor beta - metabolism
• ISSN: 0004-3591; 1529-0131
• DOI: 10.1002/1529-0131(200002)43:2<311::AID-ANR10>3.0.CO;2-E

Objective To study the effects of cyclosporin A (CSA) in a model of rheumatoid arthritis (RA) and the activation of growth factors related to pannus development at the site of injury. Methods Antigen arthritis was induced in the knees of 14 New Zealand rabbits, and the animals were randomized into 2 therapeutic groups: CSA at 10 mg/kg/day and CSA solvent. After 3 weeks of treatment, the rabbits were killed, and synovial tissues were obtained and compared with healthy specimens with regard to histopathologic lesions, deposition of transforming growth factor β (TGFβ) and collagens, and messenger RNA expression of platelet‐derived growth factor B (PDGF‐B) and TGFβ. The effect of CSA on the expression of TGFβ and PDGF‐B was also examined in cultured synovial cells. Results CSA administration alleviated the histologic damage and avoided the overdeposition of matrix elements in the injured tissue. It was also able to normalize the enhanced expression of TGFβ and PDGF‐B observed in the untreated rabbits. Despite this modulation found in vivo, CSA up‐regulated in a dose‐dependent manner the gene expression of both trophic factors by healthy cultured synovial cells. Conclusion The present study shows that continuous administration of CSA prevents the development of chronic synovitis in an experimental model of RA. As reported in other cell types, CSA promoted TGFβ transcription by synovial cells in vitro, but failed to display a profibrogenic effect in the inflamed environment.