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.
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 murineIL-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.
Authors: Klemen Strle; Robert H McCusker; Lynn Tran; Alexandra King; Rodney W Johnson; Gregory G Freund; Robert Dantzer; Keith W Kelley Journal: J Neuroimmunol Date: 2007-06-18 Impact factor: 3.478
Authors: Klemen Strle; Robert H McCusker; Rodney W Johnson; Samantha M Zunich; Robert Dantzer; Keith W Kelley Journal: Am J Physiol Endocrinol Metab Date: 2008-02-12 Impact factor: 4.310