Direct adenovirus-mediated gene transfer of interleukin 1 and tumor necrosis factor α soluble receptors to rabbit knees with experimental arthritis has local and distal anti-arthritic effects

Steven C. Ghivizzani, Eric R. Lechman, Richard Kang, Caroline Tio, Jay Kolls, Christopher H. Evans, Paul D. Robbins

Research output: Contribution to journalArticle

270 Scopus citations

Abstract

Adenoviral vectors were used to deliver genes encoding a soluble interleukin 1 (IL-1)-type I receptor-IgG fusion protein and/or a soluble type I tumor necrosis factor α (TNFα) receptor-IgG fusion protein directly to the knees of rabbits with antigen-induced arthritis. When tested individually, knees receiving the soluble IL-1 receptor had significantly reduced cartilage matrix degradation and white blood cell infiltration into the joint space. Delivery of the soluble TNFα receptor was less effective, having only a moderate effect on white blood cell infiltration and no effect on cartilage breakdown. When both soluble receptors were used together, there was a greater inhibition of white blood cell infiltration and cartilage breakdown with a considerable reduction of synovitis. Interestingly, anti- arthritic effects were also seen in contralateral control knees receiving only a marker gene, suggesting that sustained local inhibition of disease actiVity in one joint may confer an anti-arthritic effect on other joints. These results suggest that local intra-articular gene transfer could be used to treat systemic polyarticular arthritides.

Original languageEnglish (US)
Pages (from-to)4613-4618
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume95
Issue number8
DOIs
StatePublished - Apr 14 1998

ASJC Scopus subject areas

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