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

Abstract

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. 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 beta (TGFbeta) and collagens, and messenger RNA expression of platelet-derived growth factor B (PDGF-B) and TGFbeta. The effect of CSA on the expression of TGFbeta and PDGF-B was also examined in cultured synovial cells. 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 TGFbeta 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. 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 TGFbeta transcription by synovial cells in vitro, but failed to display a profibrogenic effect in the inflamed environment.