Tumor necrosis factor (TNF) is a proinflammatory
cytokine involved in the pathogenesis of
rheumatoid arthritis, and antagonism of TNF may reduce the activity of the disease. Among a number of techniques for gene transfer in vivo, the direct injection of plasmid
DNA into muscle is simple, inexpensive, and safe. In this study, we attempted to treat
collagen-induced arthritis (CIA) with anti-TNF gene therapy by transferring the plasmid encoding soluble p75
TNF receptor linked to the Fc portion of human
IgG1 (sTNFR:Fc) using in vivo electroporation. DBA/1 mice were immunized with bovine
type II collagen and boosted with the same
antigen. At 2 days after boosting, the plasmid vector containing
cDNA for the sTNFR:Fc was injected into one selected site in the gastrocnemius muscle followed by electroporation. Serum levels of sTNFR:Fc reached 2.3 ng/ml on day 5 when gene expression reached its peak. Macroscopic analysis of paws for redness, swelling and
deformities showed that the onset of moderate-to-severe CIA in mice treated with sTNFR:Fc was prevented on a significant level compared with the control mice (P<0.05). The beneficial effect of sTNFR:Fc
DNA transfer lasted for at least 18 days following treatment. In addition, both the
synovitis and the erosion of cartilage in the knee joints were dramatically reduced in mice treated with sTNFR:Fc (P<0.05). The expression of IL-1beta and
IL-12 in the paw was also decreased by sTNFR:Fc treatment (P<0.01) while there was little change in the levels of
IL-17 and vWF. These data showed that sTNFR:Fc expression plasmid was effective in the prevention of CIA, and in vivo electroporation-mediated gene transfer may provide a new approach to
cytokine therapy in autoimmune
arthritis.