Suppression of experimental arthritis by gene transfer of interleukin 1 receptor antagonist cDNA

摘要: Abstract Restoration of the impaired balance between pro- and antiinflammatory cytokines should provide effective treatment rheumatoid arthritis. Gene therapy has been proposed as an approach for delivery therapeutic proteins to arthritic joints. Here, we examined efficacy gene in bacterial cell wall-induced arthritis rats. Human secreted interleukin 1 receptor antagonist (sIL-1ra) was expressed joints rats with recurrent by using ex vivo transfer. To achieve this, primary synoviocytes were transduced culture a retroviral vector carrying sIL-1ra cDNA. Transduced cells engrafted ankle animals prior reactivation Animals control groups lacZ neo marker genes. Cells continued express transferred genes at least 9 days after engraftment. We found that transfer significantly suppressed severity recurrence arthritis, assessed measuring joint swelling gross-observation score, attenuated but did not abolish erosion cartilage bone. The effect intraarticularly essentially local, there no significant difference unengrafted contralateral experimental groups. estimate locally about four orders magnitude more therapeutically efficient than systemically administered recombinant protein. These findings evidence feasibility