Therapeutic effects of FTY720, a new immunosuppressive agent, in a murine model of acute viral myocarditis
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...
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| Veröffentlicht in: | Journal of the American College of Cardiology 2001-05, Vol.37 (6), p.1713-1718 |
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| container_title | Journal of the American College of Cardiology |
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| creator | Miyamoto, Tadashi Matsumori, Akira Hwang, Myung-Woo Nishio, Ryosuke Ito, Haruyasu Sasayama, Shigetake |
| description | 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. |
| doi_str_mv | 10.1016/S0735-1097(01)01204-9 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_70832370</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0735109701012049</els_id><sourcerecordid>70832370</sourcerecordid><originalsourceid>FETCH-LOGICAL-c471t-1e75026cef1039600902f553ef52b9a53a7bda35a807f89f6555e641bf026b823</originalsourceid><addsrcrecordid>eNqFkU1L7DAUQIMoOk_9CUpAkCdYvWmaplmJiD4FwYXjwlVI0xuN9MukHfHf23EG39JVNufcezkh5IDBGQOWnz-C5CJhoORfYCfAUsgStUFmTIgi4ULJTTL7QXbInxjfACAvmNomO4zxTPBCzcjb_BWD6XEcvKXoHNoh0s7Rm_mzTOGUGtriB_VNM7ZdHPs-YIx-gdS8YDucUt9ORDMG3yJtugrrpWvsOCBd-GBq2nx21oTKDz7ukS1n6oj763eXPN1cz69uk_uHf3dXl_eJzSQbEoZSQJpbdAy4ygEUpE4Ijk6kpTKCG1lWhgtTgHSFcrkQAvOMlW6yyiLlu-R4NbcP3fuIcdCNjxbr2rTYjVFLKHjKJUygWIE2dDEGdLoPvjHhUzPQy8j6O7JeFtTA9HdkrSbvcL1gLBus_lvrqhNwtAZMtKZ2wbTWxx9O5SpL5URdrCicYiw8Bh2tx9Zi5cP0Dbrq_C-HfAGa_Zef</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>70832370</pqid></control><display><type>article</type><title>Therapeutic effects of FTY720, a new immunosuppressive agent, in a murine model of acute viral myocarditis</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals Complete</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Alma/SFX Local Collection</source><creator>Miyamoto, Tadashi ; Matsumori, Akira ; Hwang, Myung-Woo ; Nishio, Ryosuke ; Ito, Haruyasu ; Sasayama, Shigetake</creator><creatorcontrib>Miyamoto, Tadashi ; Matsumori, Akira ; Hwang, Myung-Woo ; Nishio, Ryosuke ; Ito, Haruyasu ; Sasayama, Shigetake</creatorcontrib><description>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.</description><identifier>ISSN: 0735-1097</identifier><identifier>EISSN: 1558-3597</identifier><identifier>DOI: 10.1016/S0735-1097(01)01204-9</identifier><identifier>PMID: 11345389</identifier><identifier>CODEN: JACCDI</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Acute Disease ; Animals ; Biological and medical sciences ; Cardiovascular system ; Cardiovirus Infections - complications ; Disease Models, Animal ; Drug Evaluation, Preclinical ; Encephalomyocarditis virus ; Fingolimod Hydrochloride ; Humans ; Immunosuppressive Agents - pharmacology ; Immunosuppressive Agents - therapeutic use ; Interferon-gamma - analysis ; Interleukin-12 - analysis ; Interleukin-2 - analysis ; Male ; Medical sciences ; Mice ; Mice, Inbred DBA ; Miscellaneous ; Myocarditis - diagnosis ; Myocarditis - drug therapy ; Myocarditis - immunology ; Myocarditis - mortality ; Myocarditis - virology ; Nitric Oxide - analysis ; Pharmacology. Drug treatments ; Proportional Hazards Models ; Propylene Glycols - pharmacology ; Propylene Glycols - therapeutic use ; Severity of Illness Index ; Sphingosine - analogs & derivatives ; Survival Analysis ; Treatment Outcome ; Tumor Necrosis Factor-alpha - analysis</subject><ispartof>Journal of the American College of Cardiology, 2001-05, Vol.37 (6), p.1713-1718</ispartof><rights>2001 American College of Cardiology</rights><rights>2001 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c471t-1e75026cef1039600902f553ef52b9a53a7bda35a807f89f6555e641bf026b823</citedby><cites>FETCH-LOGICAL-c471t-1e75026cef1039600902f553ef52b9a53a7bda35a807f89f6555e641bf026b823</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0735109701012049$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=969427$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11345389$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Miyamoto, Tadashi</creatorcontrib><creatorcontrib>Matsumori, Akira</creatorcontrib><creatorcontrib>Hwang, Myung-Woo</creatorcontrib><creatorcontrib>Nishio, Ryosuke</creatorcontrib><creatorcontrib>Ito, Haruyasu</creatorcontrib><creatorcontrib>Sasayama, Shigetake</creatorcontrib><title>Therapeutic effects of FTY720, a new immunosuppressive agent, in a murine model of acute viral myocarditis</title><title>Journal of the American College of Cardiology</title><addtitle>J Am Coll Cardiol</addtitle><description>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.</description><subject>Acute Disease</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cardiovascular system</subject><subject>Cardiovirus Infections - complications</subject><subject>Disease Models, Animal</subject><subject>Drug Evaluation, Preclinical</subject><subject>Encephalomyocarditis virus</subject><subject>Fingolimod Hydrochloride</subject><subject>Humans</subject><subject>Immunosuppressive Agents - pharmacology</subject><subject>Immunosuppressive Agents - therapeutic use</subject><subject>Interferon-gamma - analysis</subject><subject>Interleukin-12 - analysis</subject><subject>Interleukin-2 - analysis</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred DBA</subject><subject>Miscellaneous</subject><subject>Myocarditis - diagnosis</subject><subject>Myocarditis - drug therapy</subject><subject>Myocarditis - immunology</subject><subject>Myocarditis - mortality</subject><subject>Myocarditis - virology</subject><subject>Nitric Oxide - analysis</subject><subject>Pharmacology. Drug treatments</subject><subject>Proportional Hazards Models</subject><subject>Propylene Glycols - pharmacology</subject><subject>Propylene Glycols - therapeutic use</subject><subject>Severity of Illness Index</subject><subject>Sphingosine - analogs & derivatives</subject><subject>Survival Analysis</subject><subject>Treatment Outcome</subject><subject>Tumor Necrosis Factor-alpha - analysis</subject><issn>0735-1097</issn><issn>1558-3597</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1L7DAUQIMoOk_9CUpAkCdYvWmaplmJiD4FwYXjwlVI0xuN9MukHfHf23EG39JVNufcezkh5IDBGQOWnz-C5CJhoORfYCfAUsgStUFmTIgi4ULJTTL7QXbInxjfACAvmNomO4zxTPBCzcjb_BWD6XEcvKXoHNoh0s7Rm_mzTOGUGtriB_VNM7ZdHPs-YIx-gdS8YDucUt9ORDMG3yJtugrrpWvsOCBd-GBq2nx21oTKDz7ukS1n6oj763eXPN1cz69uk_uHf3dXl_eJzSQbEoZSQJpbdAy4ygEUpE4Ijk6kpTKCG1lWhgtTgHSFcrkQAvOMlW6yyiLlu-R4NbcP3fuIcdCNjxbr2rTYjVFLKHjKJUygWIE2dDEGdLoPvjHhUzPQy8j6O7JeFtTA9HdkrSbvcL1gLBus_lvrqhNwtAZMtKZ2wbTWxx9O5SpL5URdrCicYiw8Bh2tx9Zi5cP0Dbrq_C-HfAGa_Zef</recordid><startdate>20010501</startdate><enddate>20010501</enddate><creator>Miyamoto, Tadashi</creator><creator>Matsumori, Akira</creator><creator>Hwang, Myung-Woo</creator><creator>Nishio, Ryosuke</creator><creator>Ito, Haruyasu</creator><creator>Sasayama, Shigetake</creator><general>Elsevier Inc</general><general>Elsevier Science</general><scope>6I.</scope><scope>AAFTH</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20010501</creationdate><title>Therapeutic effects of FTY720, a new immunosuppressive agent, in a murine model of acute viral myocarditis</title><author>Miyamoto, Tadashi ; Matsumori, Akira ; Hwang, Myung-Woo ; Nishio, Ryosuke ; Ito, Haruyasu ; Sasayama, Shigetake</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c471t-1e75026cef1039600902f553ef52b9a53a7bda35a807f89f6555e641bf026b823</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Acute Disease</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Cardiovascular system</topic><topic>Cardiovirus Infections - complications</topic><topic>Disease Models, Animal</topic><topic>Drug Evaluation, Preclinical</topic><topic>Encephalomyocarditis virus</topic><topic>Fingolimod Hydrochloride</topic><topic>Humans</topic><topic>Immunosuppressive Agents - pharmacology</topic><topic>Immunosuppressive Agents - therapeutic use</topic><topic>Interferon-gamma - analysis</topic><topic>Interleukin-12 - analysis</topic><topic>Interleukin-2 - analysis</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred DBA</topic><topic>Miscellaneous</topic><topic>Myocarditis - diagnosis</topic><topic>Myocarditis - drug therapy</topic><topic>Myocarditis - immunology</topic><topic>Myocarditis - mortality</topic><topic>Myocarditis - virology</topic><topic>Nitric Oxide - analysis</topic><topic>Pharmacology. Drug treatments</topic><topic>Proportional Hazards Models</topic><topic>Propylene Glycols - pharmacology</topic><topic>Propylene Glycols - therapeutic use</topic><topic>Severity of Illness Index</topic><topic>Sphingosine - analogs & derivatives</topic><topic>Survival Analysis</topic><topic>Treatment Outcome</topic><topic>Tumor Necrosis Factor-alpha - analysis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Miyamoto, Tadashi</creatorcontrib><creatorcontrib>Matsumori, Akira</creatorcontrib><creatorcontrib>Hwang, Myung-Woo</creatorcontrib><creatorcontrib>Nishio, Ryosuke</creatorcontrib><creatorcontrib>Ito, Haruyasu</creatorcontrib><creatorcontrib>Sasayama, Shigetake</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of the American College of Cardiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Miyamoto, Tadashi</au><au>Matsumori, Akira</au><au>Hwang, Myung-Woo</au><au>Nishio, Ryosuke</au><au>Ito, Haruyasu</au><au>Sasayama, Shigetake</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Therapeutic effects of FTY720, a new immunosuppressive agent, in a murine model of acute viral myocarditis</atitle><jtitle>Journal of the American College of Cardiology</jtitle><addtitle>J Am Coll Cardiol</addtitle><date>2001-05-01</date><risdate>2001</risdate><volume>37</volume><issue>6</issue><spage>1713</spage><epage>1718</epage><pages>1713-1718</pages><issn>0735-1097</issn><eissn>1558-3597</eissn><coden>JACCDI</coden><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.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>11345389</pmid><doi>10.1016/S0735-1097(01)01204-9</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| issn | 0735-1097 1558-3597 |
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| source | MEDLINE; Elsevier ScienceDirect Journals Complete; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Acute Disease Animals Biological and medical sciences Cardiovascular system Cardiovirus Infections - complications Disease Models, Animal Drug Evaluation, Preclinical Encephalomyocarditis virus Fingolimod Hydrochloride Humans Immunosuppressive Agents - pharmacology Immunosuppressive Agents - therapeutic use Interferon-gamma - analysis Interleukin-12 - analysis Interleukin-2 - analysis Male Medical sciences Mice Mice, Inbred DBA Miscellaneous Myocarditis - diagnosis Myocarditis - drug therapy Myocarditis - immunology Myocarditis - mortality Myocarditis - virology Nitric Oxide - analysis Pharmacology. Drug treatments Proportional Hazards Models Propylene Glycols - pharmacology Propylene Glycols - therapeutic use Severity of Illness Index Sphingosine - analogs & derivatives Survival Analysis Treatment Outcome Tumor Necrosis Factor-alpha - analysis |
| title | Therapeutic effects of FTY720, a new immunosuppressive agent, in a murine model of acute viral myocarditis |
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