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Intra‐articular electrotransfer of mouse soluble tumour necrosis factor receptor in a murine model of rheumatoid arthritis
Author(s) -
Denys Anne,
Thiolat Allan,
Descamps Delphyne,
Lemeiter Delphine,
Benihoud Karim,
Bessis Nakacha,
Boissier MarieChristophe
Publication year - 2010
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/jgm.1482
Subject(s) - tumor necrosis factor alpha , rheumatoid arthritis , arthritis , synovial membrane , genetic enhancement , inflammation , receptor , medicine , cytokine , microbiology and biotechnology , immunology , cancer research , biology , gene , biochemistry
Abstract Background Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes inflammation and destruction of the joints. In the collagen‐induced arthritis mouse model of RA, we developed a nonviral gene therapy method designed to block in situ the main cytokine tumour necrosis factor (TNF)‐α Methods Electrotransfer was used to deliver a plasmid encoding extracellular domain of mouse soluble TNF‐α receptor type I fused to the Fc fragment of mouse immunoglobulin (Ig)G1 (pTNFR‐Is) corresponding to a dimeric TNF‐α soluble receptor fusion protein (mTNFR‐Is/Ig). Results Delivery of the plasmid into the knees at symptom onset improved the histological inflammation and destruction not only at the knees, but also at the ankles, indicating a local and a regional therapeutic effect. The plasmid was detected in synovial membrane and meniscus specimens from the injected joints. In the synovial membrane, 15 days post‐injection, interleukin (IL)‐17 and TNF‐α mRNAs expression were increased, whereas IL‐10 mRNA was unchanged. However, the empty plasmid exerted a pro‐inflammatory effect 30 days post‐injection. Conclusions These data indicate that local nonviral gene therapy against TNF‐α is effective, although further work is needed to decrease plasmid induced inflammation. Copyright © 2010 John Wiley & Sons, Ltd.