Suppression of antigen-induced arthritis in rabbits by ex vivo gene therapy

Kazuhiro Otani, Ioana Nita, William Macaulay, Helga I. Georgescu, Paul D. Robbins, Christopher H. Evans

Research output: Contribution to journalArticle

177 Scopus citations

Abstract

Gene therapy offers a novel approach to treating human joint diseases such as rheumatoid arthritis. In the present study, we have used the retrovirus, MFG-IRAP, to transfer the human IL-1 receptor antagonist protein (IRAP) gene to rabbits' knees and have assessed its impact on inflammatory and chondrodestructive aspects of the acute phase of antigen-induced arthritis in these joints. Surprisingly, intra-articular expression of IRAP was three- to fivefold higher in arthritic knees than in nonarthritic knees, accumulating to levels of over 20 ng/knee in the highest expressing joints. This level of expression produced a marked chondroprotective effect but a milder anti- inflammatory one. Both the increased cartilage matrix catabolism and the inhibition of matrix synthesis that occur in antigen-induced arthritis were abrogated in the presence of the IRAP gene; the latter effect was particularly strong. Of the indices of inflammation that were examined, only leukocyte influx into the joint space was inhibited, and this effect declined with time. Concentrations of rabbit IL-1 were reduced by the IRAP gene, suggesting inhibition of an autocrine induction loop. These data demonstrate that the course of arthritic disease in the rabbit knee can be altered by genetic manipulation, thus encouraging the further development of gene treatments for human joint diseases.

Original languageEnglish (US)
Pages (from-to)3558-3562
Number of pages5
JournalJournal of Immunology
Volume156
Issue number9
StatePublished - May 1 1996

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Otani, K., Nita, I., Macaulay, W., Georgescu, H. I., Robbins, P. D., & Evans, C. H. (1996). Suppression of antigen-induced arthritis in rabbits by ex vivo gene therapy. Journal of Immunology, 156(9), 3558-3562.