Cytokine gene therapy for myocarditis by in vivo electroporation

A. Nakano, A. Matsumori, Shunsuke Kawamoto, H. Tahara, E. Yamato, S. Sasayama, J. I. Miyazaki

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Abstract

Cytokines are important pathophysiologic and pathogenic factors in cardiovascular disorders, including viral myocarditis. We attempted to treat viral myocarditis with cytokine gene therapy by transferring an inhibitory cytokine, IL-1 receptor antagonist (IL-1ra) or viral IL-10 (vIL-10), by in vivo electroporation, a new method for gene transfer into muscle. Four-week-old male DBA/2 mice were inoculated intraperitoneally with 10 PFU of encephalomyocarditis virus. Immediately after virus inoculation, an expression plasmid carrying IL-1ra or vIL-10 was injected into tibialis anterior muscles followed by electroporation. Serum levels of IL-1ra and vIL-10 reached 10.5 and 2.3 ng/ml, respectively, on day 5, when gene expression reached its peak. Histopathological examination showed that myocardial cellular infiltration was improved in mice treated with IL-1ra or vIL-10 compared with the control group. On day 14 after the onset of myocarditis, transfer of IL-1ra or vIL-10 expression plasmid had significantly improved the survival rates of the animals. The expression of TNF-α was decreased to 0.60-fold (p < 0.005) and inducible nitric oxide synthase (iNOS) 0.43-fold (p < 0.005) by IL-1ra treatment, and the expression of IFN-γ in the heart was decreased to 0.35-fold (p < 0.05), and iNOS 0.21-fold (p < 0.005), by vIL-10 relative to the controls. These results show that gene therapy with IL-1ra or vIL-10 expression plasmid was effective in the treatment of viral myocarditis, and in vivo electroporation may be a useful method by which to deliver cytokine therapy in cardiovascular diseases.

Original languageEnglish
Pages (from-to)1289-1297
Number of pages9
JournalHuman Gene Therapy
Volume12
Issue number10
DOIs
Publication statusPublished - 2001 Aug 7

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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    Nakano, A., Matsumori, A., Kawamoto, S., Tahara, H., Yamato, E., Sasayama, S., & Miyazaki, J. I. (2001). Cytokine gene therapy for myocarditis by in vivo electroporation. Human Gene Therapy, 12(10), 1289-1297. https://doi.org/10.1089/104303401750270940