TNFR-Fc fusion protein expressed by in vivo electroporation improves survival rates and myocardial injury in coxsackievirus induced murine myocarditis

Biochem Biophys Res Commun. 2006 Jun 9;344(3):765-71. doi: 10.1016/j.bbrc.2006.03.170. Epub 2006 Apr 5.

Abstract

Tumor necrosis factor-alpha (TNF-alpha) is one of the major cytokines that modulate the immune response in viral myocarditis, but its role has not yet been thoroughly evaluated. We antagonized TNF-alpha using the expressed soluble p75 TNF receptor linked to the Fc portion of the human IgG1 gene (sTNFR:Fc) by in vivo electroporation, and evaluated its effects on experimental coxsackieviral B3 (CVB3) myocarditis. A plasmid DNA encoding sTNFR:Fc (15microg/mouse) was injected into the gastrocnemius muscles of Balb/C male mice followed by electroporation (day -1). Control mice were injected with an empty vector. One day after electroporation, mice were infected with CVB3 (day 0). Serum levels of sTNFR:Fc increased from day 2 and peaked at day 5 following electroporation. The heart virus titers of sTNFR:Fc mice were higher than those of controls at day 3. However, subsequent to day 12, the survival rates of the sTNFR:Fc mice were significantly higher than those of the controls (36% versus 0% at day 27, P<0.01). Histopathological examination indicated that inflammation and myocardial fibrosis were significantly decreased in sTNFR:Fc mice at day 12. The expressed sTNFR:Fc could modulate the inflammatory process during the post-viremic phase of viral myocarditis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Coxsackievirus Infections / metabolism
  • Coxsackievirus Infections / pathology*
  • Coxsackievirus Infections / therapy*
  • Electroporation / methods
  • Genetic Therapy / methods
  • Immunoglobulin G / administration & dosage*
  • Immunoglobulin G / genetics
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Myocarditis / metabolism
  • Myocarditis / pathology*
  • Myocarditis / therapy*
  • Myocarditis / virology
  • Receptors, Tumor Necrosis Factor / administration & dosage*
  • Receptors, Tumor Necrosis Factor / genetics*
  • Recombinant Fusion Proteins / administration & dosage
  • Survival Analysis
  • Survival Rate
  • Transfection / methods
  • Treatment Outcome

Substances

  • Immunoglobulin G
  • Receptors, Tumor Necrosis Factor
  • Recombinant Fusion Proteins