HUMAN IL-1RA GENE-TRANSFER INTO HUMAN SYNOVIAL FIBROBLASTS IS CHONDROPROTECTIVE

Rheumatoid arthritis (RA) is characterized by progressive destruction of synovial cartilage. In vitro, degradation of cartilage is stimulate d by IL-1, a proinflammatory cytokine, which is released from RA synov ial fibroblasts (RA-SF), To determine whether gene therapy using the g ene encoding the naturally occurring inhibitor of IL-1, IL-1 receptor antagonist (IL-1Ra) is feasible, IL-1Ra-transduced RA-SF were coimplan ted with normal human cartilage in SCID mice, The IL-1Ra-transduced RA -SF continued to secrete IL-1Ra over a 60-day period. Cartilage that w as coimplanted with RA-SF transduced with a marker gene exhibited prog ressive, chondrocyte-mediated cartilage degradation, whereas no such d egradation was observed in cartilage that was coimplanted with RA-SF t ransduced with IL-1Ra. Thus, gene therapy using a retrovirus-based gen e delivery system appears to be a feasible approach to effectively mod ifying the local synovial environment.