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 stimulated by IL-1, a proinflammatory cytokine, which is released from RA synovial fibroblasts (RA-SF). To determine whether gene therapy using the gene encoding the naturally occurring inhibitor of IL-1, IL-1 receptor antagonist (IL-1Ra) is feasible, IL-1 Ra-transduced RA-SF were coimplanted with normal human cartilage in SCID mice. The IL-1 Ra-transduced RA-SF continued to secrete IL-1Ra over a 60-day period. Cartilage that was coimplanted with RA-SF transduced with a marker gene exhibited progressive, chondrocyte-mediated cartilage degradation, whereas no such degradation was observed in cartilage that was coimplanted with RA-SF transduced with IL-1 Ra. Thus, gene therapy using a retrovirus-based gene delivery system appears to be a feasible approach to effectively modifying the local synovial environment.
Müller-Ladner
U
U
Department of Medicine, University of Alabama at Birmingham 35294, USA.
Roberts
C R
CR
Franklin
B N
BN
Gay
R E
RE
Robbins
P D
PD
Evans
C H
CH
Gay
S
S
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D002358:Cartilage, Articular / Q000276:immunology / Q000473:pathology* / Q000637:transplantation; D002478:Cells, Cultured; D005347:Fibroblasts / Q000276:immunology / Q000637:transplantation; D018014:Gene Transfer Techniques; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D017472:Receptors, Interleukin-1 / Q000235:genetics* / Q000502:physiology*; D013583:Synovial Membrane / Q000276:immunology* / Q000473:pathology / Q000637:transplantation
D017472:Receptors, Interleukin-1