doi: 10.1161/hc3501.096190
(Circulation. 2001;104:1098.)
© 2001 American Heart Association, Inc.
Brief Rapid Communications |
Protection Against Autoimmune Myocarditis by Gene Transfer of Interleukin-10 by Electroporation
From the Department of Clinical Pharmacology (K.W.) and the Department of Pharmacology (T.O.), Niigata College of Pharmacy; the Department of Medical Technology, School of Health Sciences, Niigata University School of Medicine (M.N.); the Division of Cardiology (K.F., H.H., M.K., Y.A.) and the Division of Clinical Nephrology and Rheumatology (F.G., H.M.), Niigata Graduate School of Medicine and Dental Science, Niigata, Japan; and the Department of Nutrition and Physiological Chemistry, Osaka University Graduate School of Medicine, Osaka, Japan (J.M.).
Correspondence to Kenichi Watanabe, MD, Department of Clinical Pharmacology, Niigata College of Pharmacy, Kamisin-ei-cho, Niigata, 950-2081, Japan. E-mail watanabe{at}niigata-pharm.ac.jp
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.
Methods and 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 µg 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.
Key Words: interleukins • myocarditis • gene therapy • immune system • cardiomyopathy
This article has been cited by other articles:
 |
|
 |
|
  K. Li, W. Xu, Q. Guo, Z. Jiang, P. Wang, Y. Yue, and S. Xiong Differential Macrophage Polarization in Male and Female BALB/c Mice Infected With Coxsackievirus B3 Defines Susceptibility to Viral Myocarditis Circ. Res., August 14, 2009; 105(4): 353 - 364. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Szalay, M. Sauter, J. Hald, A. Weinzierl, R. Kandolf, and K. Klingel Sustained Nitric Oxide Synthesis Contributes to Immunopathology in Ongoing Myocarditis Attributable to Interleukin-10 Disorders Am. J. Pathol., December 1, 2006; 169(6): 2085 - 2093. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Chang, H. Hanawa, H. Liu, T. Yoshida, M. Hayashi, R. Watanabe, S. Abe, K. Toba, K. Yoshida, R. Elnaggar, et al. Hydrodynamic-Based Delivery of an Interleukin-22-Ig Fusion Gene Ameliorates Experimental Autoimmune Myocarditis in Rats J. Immunol., September 15, 2006; 177(6): 3635 - 3643. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Nishii, T. Inomata, H. Niwano, H. Takehana, I. Takeuchi, H. Nakano, H. Shinagawa, T. Naruke, T. Koitabashi, J.-i. Nakahata, et al. {beta}2-Adrenergic Agonists Suppress Rat Autoimmune Myocarditis: Potential Role of {beta}2-Adrenergic Stimulants as New Therapeutic Agents for Myocarditis Circulation, August 29, 2006; 114(9): 936 - 944. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Kosuge, G. Haraguchi, N. Koga, Y. Maejima, J.-i. Suzuki, and M. Isobe Pioglitazone Prevents Acute and Chronic Cardiac Allograft Rejection Circulation, June 6, 2006; 113(22): 2613 - 2622. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Yoshida, H. Hanawa, K. Toba, H. Watanabe, R. Watanabe, K. Yoshida, S. Abe, K. Kato, M. Kodama, and Y. Aizawa Expression of immunological molecules by cardiomyocytes and inflammatory and interstitial cells in rat autoimmune myocarditis Cardiovasc Res, November 1, 2005; 68(2): 278 - 288. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Futamatsu, J.-i. Suzuki, S. Mizuno, N. Koga, S. Adachi, H. Kosuge, Y. Maejima, K. Hirao, T. Nakamura, and M. Isobe Hepatocyte Growth Factor Ameliorates the Progression of Experimental Autoimmune Myocarditis: A Potential Role for Induction of T Helper 2 Cytokines Circ. Res., April 29, 2005; 96(8): 823 - 830. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Fuse, M. Kodama, Y. Okura, M. Ito, K. Kato, H. Hanawa, and Y. Aizawa Short-term prognostic value of initial serum levels of interleukin-10 in patients with acute myocarditis Eur J Heart Fail, January 1, 2005; 7(1): 109 - 112. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Nishii, T. Inomata, H. Takehana, I. Takeuchi, H. Nakano, T. Koitabashi, J.-i. Nakahata, N. Aoyama, and T. Izumi Serum levels of interleukin-10 on admission as a prognostic predictor of human fulminant myocarditis J. Am. Coll. Cardiol., September 15, 2004; 44(6): 1292 - 1297. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. U. Knowlton and T. Yajima Interleukin-10: Biomarker or pathologic cytokine in fulminant myocarditis? J. Am. Coll. Cardiol., September 15, 2004; 44(6): 1298 - 1300. [Full Text] [PDF]
|
|
|
|
 |
|
 K. Komamura, R. Tatsumi, J.-i. Miyazaki, K. Matsumoto, E. Yamato, T. Nakamura, Y. Shimizu, T. Nakatani, S. Kitamura, H. Tomoike, et al. Treatment of Dilated Cardiomyopathy With Electroporation of Hepatocyte Growth Factor Gene Into Skeletal Muscle Hypertension, September 1, 2004; 44(3): 365 - 371. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Li, J. S. Heuser, S. D. Kosanke, M. Hemric, and M. W. Cunningham Cryptic Epitope Identified in Rat and Human Cardiac Myosin S2 Region Induces Myocarditis in the Lewis Rat J. Immunol., March 1, 2004; 172(5): 3225 - 3234. [Abstract] [Full Text] [PDF]
|
|