Protection against autoimmune myocarditis by gene transfer of interleukin-10 by electroporation.
BACKGROUND
Although immunosuppressive therapy for myocarditis has attracted a great deal of attention, its effectiveness is controversial. Interleukin (IL)-10 has a variety of immunomodulatory properties. Among the nonviral techniques for gene transfer in vivo, the direct injection of plasmid DNA into muscle is simple, inexpensive, and safe.


RESULTS
We examined the applicability of murine IL-10 (mIL-10) gene transfer to the treatment of rats with experimental autoimmune myocarditis. Nine-week-old Lewis rats were inoculated with pig myosin (day 0). A plasmid vector expressing mIL-10 cDNA (800 microgram per rat) was transferred into the tibialis anterior muscles by electroporation 3 times (5 days before immunization and at days 4 and 13); control rats received empty plasmid. Electroporation increased the serum mIL-10 levels to >250 pg/mL. The 21-day survival rate in rats treated with mIL-10 cDNA was higher (15 of 15; 100%) than that of the control group (9 of 15; 60%). Furthermore, mIL-10 treatment significantly attenuated myocardial lesions and improved hemodynamic parameters.


CONCLUSIONS
These findings showed that gene transfer into muscle by electroporation in vivo is an effective means of delivery of IL-10 for the treatment of autoimmune myocarditis.
Watanabe
K
K
Department of Clinical Pharmacology, Niigata College of Pharmacy, Japan. watanabe@niigata-pharm.ac.jp
Nakazawa
M
M
Fuse
K
K
Hanawa
H
H
Kodama
M
M
Aizawa
Y
Y
Ohnuki
T
T
Gejyo
F
F
Maruyama
H
H
Miyazaki
J
J
D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000517:prevention & control*; D001835:Body Weight / Q000187:drug effects; D018274:Electroporation; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D006439:Hemodynamics / Q000187:drug effects; D016753:Interleukin-10 / Q000008:administration & dosage / Q000097:blood / Q000235:genetics*; D051379:Mice; D009205:Myocarditis / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000276:immunology / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics; D051381:Rats; D011917:Rats, Inbred Lew; D013552:Swine; D013997:Time Factors
D016753:Interleukin-10