Human IL-1Ra Gene Transfer into Human Synovial Fibroblasts Is Chondroprotective

Ulf Müller-Ladner, Charles R. Roberts, Barry N. Franklin, Renate E. Gay, Paul D. Robbins, Christopher H. Evans, Steffen Gay

Research output: Contribution to journalArticle

141 Scopus citations

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-1Ra-transduced RA-SF were coimplanted 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 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-1Ra. Thus, gene therapy using a retrovirus-based gene delivery system appears to be a feasible approach to effectively modifying the local synovial environment.

Original languageEnglish (US)
Pages (from-to)3492-3498
Number of pages7
JournalJournal of Immunology
Volume158
Issue number7
StatePublished - Apr 1 1997

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Müller-Ladner, U., Roberts, C. R., Franklin, B. N., Gay, R. E., Robbins, P. D., Evans, C. H., & Gay, S. (1997). Human IL-1Ra Gene Transfer into Human Synovial Fibroblasts Is Chondroprotective. Journal of Immunology, 158(7), 3492-3498.