Efficacy of interleukin-10 gene electrotransfer into skeletal muscle in mice with collagen-induced arthritis.
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.
Saidenberg-Kermanac'h
Nathalie
N
UPRES EA-3408 and Department of Rheumatology, Claude Bernard Foundation, Medical School of Bobigny, University of Paris 13, France.
Bessis
Natacha
N
Deleuze
Virginie
V
Bloquel
Carole
C
Bureau
Michel
M
Scherman
Daniel
D
Boissier
Marie-Christophe
MC
D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D004563:Electrochemistry; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics* / Q000276:immunology; D007719:Knee Joint / Q000166:cytology / Q000473:pathology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D018482:Muscle, Skeletal / Q000502:physiology*; D010957:Plasmids / Q000235:genetics / Q000378:metabolism
D016753:Interleukin-10