Abstract
Background
Gene therapy is very promising in the treatment of rheumatoid arthritis (RA). Electrotransfer is a recent method reported to enhance in vivo intramuscular DNA transfection. Interleukin‐10 (IL‐10) has antiinflammatory effects in RA and in collagen‐induced arthritis (CIA), a murine model of RA. In order to improve our strategy of gene therapy, we used electrotransfer to enhance penetration into skeletal muscle with CIA of plasmids encoding IL‐10.
Methods
CIA was induced in DBA/1 mice by immunization with bovine type II collagen. Injection into the tibial cranial muscle of low‐dose (200 ng) pCOR plasmid encoding murine IL‐10 (pCOR‐CMV‐mIL‐10) was immediately followed by application of square‐wave electric pulses (8 pulses of 200V/cm, 20 ms duration at 2 Hz). Control groups received empty plasmid or saline before electrotransfer.
Results
When electrotransfer was performed twice on days 10 and 25 postimmunization, CIA was significantly delayed (P < 0.05) and attenuated (P < 0.001) in groups treated by electrotransfer or pCOR‐CMV‐mIL‐10 plasmid vs. control groups. When electrotransfer of pCOR‐CMV‐mIL‐10 plasmid was performed on days 25 and 40 postimmunization, at disease onset, the clinical severity of CIA was reduced (P < 0.05). All groups which had been electrotransferred early or late by pCOR‐CMV‐mIL‐10 plasmid showed suppression of histological signs of arthritis.
Conclusions
Taken together, these data indicate that administration of an antiinflammatory plasmid‐born gene by electrotransfer of naked DNA is effective in vivo in an arthritis model. Copyright © 2002 John Wiley & Sons, Ltd.