THU0124 Autologous fibroblasts as vectors for anti_inflammatory gene therapy in murine collagen-induced arthritis

Background No treatments effective in the long term are available for rheumatoid arthritis. Objectives Recent advances in gene therapy and cell therapy have prompted us to design for collagen-induced arthritis (CIA), a new treatment strategy involving injection of autologous fibroblasts transfected with the IL-4 gene using a nonviral method. Methods A line of immortalised fibroblasts from DBA/1 mice (DBA/1/0 cells) were transfected with a plasmid expressing IL-4 cDNA (DBA/1/IL-4 cells). Xenogeneic fibroblasts from Chinese hamster ovary (CHO) transfected with a plasmid expressing murine IL-4 cDNA were studied also. CIA was caused in DBA/1 mice by injecting bovine type II collagen (CIIB). The cells were injected into the subcutaneous tissue of the back 10 and 25 days after immunisation of the mice by 3. 106 DBA/1/0 or DBA/1/IL-4 or CHO/IL-4 cells. Results Injection of DBA/1/IL-4 cells was associated with a significant and lasting improvement in the clinical and histological evidence of joint inflammation and destruction as compared with DBA/1/0 cells and CHO/IL-4 cells. The mice injected with DBA/1/IL-4 cells showed decreases in the production of IgG2a antibody to CII and in the proliferation of CIIB-specific nodal T cells. Conclusion Taken in aggregate, these findings indicate that grafting autologous cells transfected with a gene encoding an antiinflammatory cytokine is effective in CIA and may attenuate the cytokine imbalance seen in this disease. Rheumatoid Arthritis – Clinical aspects