TNFR-Fc fusion protein expressed by in vivo electroporation improves survival rates and myocardial injury in coxsackievirus induced murine myocarditis.
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.
Kim
Jong-Mook
JM
ViroMed Co. Ltd, Seoul, Republic of Korea.
Lim
Byung-Kwan
BK
Ho
Seong-Hyun
SH
Yun
Soo-Hyeon
SH
Shin
Jae-Ok
JO
Park
Eun-Min
EM
Kim
Duk-Kyung
DK
Kim
Sunyoung
S
Jeon
Eun-Seok
ES
D000818:Animals; D003384:Coxsackievirus Infections / Q000378:metabolism / Q000473:pathology* / Q000628:therapy*; D018274:Electroporation / Q000379:methods; D015316:Genetic Therapy / Q000379:methods; D007074:Immunoglobulin G / Q000008:administration & dosage* / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000378:metabolism / Q000473:pathology* / Q000628:therapy* / Q000821:virology; D018124:Receptors, Tumor Necrosis Factor / Q000008:administration & dosage* / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage; D016019:Survival Analysis; D015996:Survival Rate; D014162:Transfection / Q000379:methods; D016896:Treatment Outcome
D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins