PMID- 16631119 OWN - NLM STAT- MEDLINE DCOM- 20060622 LR - 20121115 IS - 0006-291X (Print) IS - 0006-291X (Linking) VI - 344 IP - 3 DP - 2006 Jun 9 TI - TNFR-Fc fusion protein expressed by in vivo electroporation improves survival rates and myocardial injury in coxsackievirus induced murine myocarditis. PG - 765-71 AB - 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. FAU - Kim, Jong-Mook AU - Kim JM AD - ViroMed Co. Ltd, Seoul, Republic of Korea. FAU - Lim, Byung-Kwan AU - Lim BK FAU - Ho, Seong-Hyun AU - Ho SH FAU - Yun, Soo-Hyeon AU - Yun SH FAU - Shin, Jae-Ok AU - Shin JO FAU - Park, Eun-Min AU - Park EM FAU - Kim, Duk-Kyung AU - Kim DK FAU - Kim, Sunyoung AU - Kim S FAU - Jeon, Eun-Seok AU - Jeon ES LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20060405 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Immunoglobulin G) RN - 0 (Receptors, Tumor Necrosis Factor) RN - 0 (Recombinant Fusion Proteins) SB - IM MH - Animals MH - Coxsackievirus Infections/metabolism/*pathology/*therapy MH - Electroporation/methods MH - Genetic Therapy/methods MH - Immunoglobulin G/*administration & dosage/genetics MH - Male MH - Mice MH - Mice, Inbred BALB C MH - Myocarditis/metabolism/*pathology/*therapy/virology MH - Receptors, Tumor Necrosis Factor/*administration & dosage/*genetics MH - Recombinant Fusion Proteins/administration & dosage MH - Survival Analysis MH - Survival Rate MH - Transfection/methods MH - Treatment Outcome EDAT- 2006/04/25 09:00 MHDA- 2006/06/23 09:00 CRDT- 2006/04/25 09:00 PHST- 2006/03/13 00:00 [received] PHST- 2006/03/22 00:00 [accepted] PHST- 2006/04/25 09:00 [pubmed] PHST- 2006/06/23 09:00 [medline] PHST- 2006/04/25 09:00 [entrez] AID - S0006-291X(06)00679-6 [pii] AID - 10.1016/j.bbrc.2006.03.170 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2006 Jun 9;344(3):765-71. doi: 10.1016/j.bbrc.2006.03.170. Epub 2006 Apr 5.