Therapeutic effects of FTY720, a new immunosuppressive agent, in a murine model of acute viral myocarditis

Giuseppe Stabile, Antonio De Simone, Pietro Turco, Vincenzo La Rocca, Pasquale Nocerino, Costantino Astarita, Francesco Maresca, Carmine De Matteis, Tommaso Di Napoli, Eugenio Stabile, Dino Franco Vitale

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Abstract

OBJECTIVES: This study examines the efficacy of FTY720 (FTY), a new immunosuppressor, in the treatment of acute viral myocarditis in a murine model. BACKGROUND: Immunosuppressive agents have no proven therapeutic efficacy in experimental or clinical myocarditis. METHODS: Encephalomyocarditis virus was inoculated i.p. in DBA/2 mice on day 0. Postinoculation treatment consisted of FTY 10 mg/kg/day p.o. (FTY group), or cyclosporine A (CsA) 40 mg/kg/day p.o. (CsA group) or distilled water p.o. only (control group). Survival until day 14, as well as cardiac histopathology, virus concentrations, cytokines (interleukin [IL]-2, IL-12, interferon [IFN]-gamma and tumor necrosis factor [TNF]-alpha) and nitric oxide (NO) on day 5 were examined. RESULTS: In the control and CsA groups, all mice died within 10 and 7 days, respectively. However, in the FTY group, 27% of the animals survived up to day 14. Compared with the control group, 1) histological scores were significantly lower in the FTY group but unchanged in the CsA group; 2) virus concentration was significantly higher in the CsA group but not in the FTY group; 3) expressions of IL-2, IL-12 and IFN-gamma in the heart were suppressed in both the FTY and CsA groups, though suppression was weaker in the FTY group; 4) TNF-alpha and NO were significantly increased in the CsA group but not in the FTY group. CONCLUSIONS: FTY720 had a significant therapeutic effect in acute experimental myocarditis without inducing excessive virus replication. This report is the first to describe a beneficial effect by an immunosuppressive agent in the treatment of acute viral myocarditis.

Original languageEnglish
Pages (from-to)1713-1718
Number of pages6
JournalJournal of the American College of Cardiology
Volume37
Issue number6
DOIs
Publication statusPublished - 2001

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Myocarditis
Therapeutic Uses
Immunosuppressive Agents
Cyclosporine
Interleukin-12
Interferon-gamma
Interleukin-2
Nitric Oxide
Tumor Necrosis Factor-alpha
Fingolimod Hydrochloride
Encephalomyocarditis virus
Viruses
Control Groups
Inbred DBA Mouse
Virus Replication
Cytokines
Water

ASJC Scopus subject areas

  • Nursing(all)

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Therapeutic effects of FTY720, a new immunosuppressive agent, in a murine model of acute viral myocarditis. / Stabile, Giuseppe; De Simone, Antonio; Turco, Pietro; La Rocca, Vincenzo; Nocerino, Pasquale; Astarita, Costantino; Maresca, Francesco; De Matteis, Carmine; Di Napoli, Tommaso; Stabile, Eugenio; Vitale, Dino Franco.

In: Journal of the American College of Cardiology, Vol. 37, No. 6, 2001, p. 1713-1718.

Research output: Contribution to journalArticle

Stabile, G, De Simone, A, Turco, P, La Rocca, V, Nocerino, P, Astarita, C, Maresca, F, De Matteis, C, Di Napoli, T, Stabile, E & Vitale, DF 2001, 'Therapeutic effects of FTY720, a new immunosuppressive agent, in a murine model of acute viral myocarditis', Journal of the American College of Cardiology, vol. 37, no. 6, pp. 1713-1718. https://doi.org/10.1016/S0735-1097(01)01204-9
Stabile, Giuseppe ; De Simone, Antonio ; Turco, Pietro ; La Rocca, Vincenzo ; Nocerino, Pasquale ; Astarita, Costantino ; Maresca, Francesco ; De Matteis, Carmine ; Di Napoli, Tommaso ; Stabile, Eugenio ; Vitale, Dino Franco. / Therapeutic effects of FTY720, a new immunosuppressive agent, in a murine model of acute viral myocarditis. In: Journal of the American College of Cardiology. 2001 ; Vol. 37, No. 6. pp. 1713-1718.
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abstract = "OBJECTIVES: This study examines the efficacy of FTY720 (FTY), a new immunosuppressor, in the treatment of acute viral myocarditis in a murine model. BACKGROUND: Immunosuppressive agents have no proven therapeutic efficacy in experimental or clinical myocarditis. METHODS: Encephalomyocarditis virus was inoculated i.p. in DBA/2 mice on day 0. Postinoculation treatment consisted of FTY 10 mg/kg/day p.o. (FTY group), or cyclosporine A (CsA) 40 mg/kg/day p.o. (CsA group) or distilled water p.o. only (control group). Survival until day 14, as well as cardiac histopathology, virus concentrations, cytokines (interleukin [IL]-2, IL-12, interferon [IFN]-gamma and tumor necrosis factor [TNF]-alpha) and nitric oxide (NO) on day 5 were examined. RESULTS: In the control and CsA groups, all mice died within 10 and 7 days, respectively. However, in the FTY group, 27{\%} of the animals survived up to day 14. Compared with the control group, 1) histological scores were significantly lower in the FTY group but unchanged in the CsA group; 2) virus concentration was significantly higher in the CsA group but not in the FTY group; 3) expressions of IL-2, IL-12 and IFN-gamma in the heart were suppressed in both the FTY and CsA groups, though suppression was weaker in the FTY group; 4) TNF-alpha and NO were significantly increased in the CsA group but not in the FTY group. CONCLUSIONS: FTY720 had a significant therapeutic effect in acute experimental myocarditis without inducing excessive virus replication. This report is the first to describe a beneficial effect by an immunosuppressive agent in the treatment of acute viral myocarditis.",
author = "Giuseppe Stabile and {De Simone}, Antonio and Pietro Turco and {La Rocca}, Vincenzo and Pasquale Nocerino and Costantino Astarita and Francesco Maresca and {De Matteis}, Carmine and {Di Napoli}, Tommaso and Eugenio Stabile and Vitale, {Dino Franco}",
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T1 - Therapeutic effects of FTY720, a new immunosuppressive agent, in a murine model of acute viral myocarditis

AU - Stabile, Giuseppe

AU - De Simone, Antonio

AU - Turco, Pietro

AU - La Rocca, Vincenzo

AU - Nocerino, Pasquale

AU - Astarita, Costantino

AU - Maresca, Francesco

AU - De Matteis, Carmine

AU - Di Napoli, Tommaso

AU - Stabile, Eugenio

AU - Vitale, Dino Franco

PY - 2001

Y1 - 2001

N2 - OBJECTIVES: This study examines the efficacy of FTY720 (FTY), a new immunosuppressor, in the treatment of acute viral myocarditis in a murine model. BACKGROUND: Immunosuppressive agents have no proven therapeutic efficacy in experimental or clinical myocarditis. METHODS: Encephalomyocarditis virus was inoculated i.p. in DBA/2 mice on day 0. Postinoculation treatment consisted of FTY 10 mg/kg/day p.o. (FTY group), or cyclosporine A (CsA) 40 mg/kg/day p.o. (CsA group) or distilled water p.o. only (control group). Survival until day 14, as well as cardiac histopathology, virus concentrations, cytokines (interleukin [IL]-2, IL-12, interferon [IFN]-gamma and tumor necrosis factor [TNF]-alpha) and nitric oxide (NO) on day 5 were examined. RESULTS: In the control and CsA groups, all mice died within 10 and 7 days, respectively. However, in the FTY group, 27% of the animals survived up to day 14. Compared with the control group, 1) histological scores were significantly lower in the FTY group but unchanged in the CsA group; 2) virus concentration was significantly higher in the CsA group but not in the FTY group; 3) expressions of IL-2, IL-12 and IFN-gamma in the heart were suppressed in both the FTY and CsA groups, though suppression was weaker in the FTY group; 4) TNF-alpha and NO were significantly increased in the CsA group but not in the FTY group. CONCLUSIONS: FTY720 had a significant therapeutic effect in acute experimental myocarditis without inducing excessive virus replication. This report is the first to describe a beneficial effect by an immunosuppressive agent in the treatment of acute viral myocarditis.

AB - OBJECTIVES: This study examines the efficacy of FTY720 (FTY), a new immunosuppressor, in the treatment of acute viral myocarditis in a murine model. BACKGROUND: Immunosuppressive agents have no proven therapeutic efficacy in experimental or clinical myocarditis. METHODS: Encephalomyocarditis virus was inoculated i.p. in DBA/2 mice on day 0. Postinoculation treatment consisted of FTY 10 mg/kg/day p.o. (FTY group), or cyclosporine A (CsA) 40 mg/kg/day p.o. (CsA group) or distilled water p.o. only (control group). Survival until day 14, as well as cardiac histopathology, virus concentrations, cytokines (interleukin [IL]-2, IL-12, interferon [IFN]-gamma and tumor necrosis factor [TNF]-alpha) and nitric oxide (NO) on day 5 were examined. RESULTS: In the control and CsA groups, all mice died within 10 and 7 days, respectively. However, in the FTY group, 27% of the animals survived up to day 14. Compared with the control group, 1) histological scores were significantly lower in the FTY group but unchanged in the CsA group; 2) virus concentration was significantly higher in the CsA group but not in the FTY group; 3) expressions of IL-2, IL-12 and IFN-gamma in the heart were suppressed in both the FTY and CsA groups, though suppression was weaker in the FTY group; 4) TNF-alpha and NO were significantly increased in the CsA group but not in the FTY group. CONCLUSIONS: FTY720 had a significant therapeutic effect in acute experimental myocarditis without inducing excessive virus replication. This report is the first to describe a beneficial effect by an immunosuppressive agent in the treatment of acute viral myocarditis.

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