title: Human IL-1Ra gene transfer into human synovial fibroblasts is chondroprotective.
abstract: 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.
authors.affiliation: Department of Medicine, University of Alabama at Birmingham 35294, USA.
authors.forename: U
authors.initials: U
authors.lastname: Müller-Ladner
authors.forename: C R
authors.initials: CR
authors.lastname: Roberts
authors.forename: B N
authors.initials: BN
authors.lastname: Franklin
authors.forename: R E
authors.initials: RE
authors.lastname: Gay
authors.forename: P D
authors.initials: PD
authors.lastname: Robbins
authors.forename: C H
authors.initials: CH
authors.lastname: Evans
authors.forename: S
authors.initials: S
authors.lastname: Gay
mesh_terms: 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
chemical_list: D017472:Receptors, Interleukin-1