Phenytoin at optimum doses ameliorates experimental autoimmune encephalomyelitis via modulation of immunoregulatory cells
Abstract We investigated the optimum doses of phenytoin for treatment of myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (EAE). Oral and intraperitoneal administrations of 0.25 to 1.0 mg per mouse (12.5–50 mg/kg) 3 times a week improved the clinical course. Intr...
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| Veröffentlicht in: | Journal of neuroimmunology 2011-04, Vol.233 (1), p.112-119 |
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| container_title | Journal of neuroimmunology |
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| creator | Hashiba, Naomi Nagayama, Shigemi Araya, Shin-ich Inada, Hiroyuki Sonobe, Yoshifumi Suzumura, Akio Matsui, Makoto |
| description | Abstract We investigated the optimum doses of phenytoin for treatment of myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (EAE). Oral and intraperitoneal administrations of 0.25 to 1.0 mg per mouse (12.5–50 mg/kg) 3 times a week improved the clinical course. Intraperitoneal injections of 1.0 mg phenytoin were the most effective, as a significant reduction in EAE severity was seen after only 2 administrations with that protocol. Treatment efficacy was associated with amelioration of cellular infiltrates in the CNS, and an increase in CD4+ Foxp3+ and CD4+ CD25+ CD127− regulatory T cells as well as CD8+ suppressor/cytotoxic T cells in blood. |
| doi_str_mv | 10.1016/j.jneuroim.2010.12.006 |
| format | Article |
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Oral and intraperitoneal administrations of 0.25 to 1.0 mg per mouse (12.5–50 mg/kg) 3 times a week improved the clinical course. Intraperitoneal injections of 1.0 mg phenytoin were the most effective, as a significant reduction in EAE severity was seen after only 2 administrations with that protocol. Treatment efficacy was associated with amelioration of cellular infiltrates in the CNS, and an increase in CD4+ Foxp3+ and CD4+ CD25+ CD127− regulatory T cells as well as CD8+ suppressor/cytotoxic T cells in blood.</description><identifier>ISSN: 0165-5728</identifier><identifier>EISSN: 1872-8421</identifier><identifier>DOI: 10.1016/j.jneuroim.2010.12.006</identifier><identifier>PMID: 21237519</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Allergy and Immunology ; Animals ; Anticonvulsants - therapeutic use ; CD127 ; CD8 ; Disease Models, Animal ; EAE ; Encephalomyelitis, Autoimmune, Experimental - drug therapy ; Encephalomyelitis, Autoimmune, Experimental - immunology ; Encephalomyelitis, Autoimmune, Experimental - pathology ; Immunologic Factors - therapeutic use ; Mice ; Mice, Inbred C57BL ; Neurology ; Phenytoin ; Phenytoin - therapeutic use ; Regulatory T cells ; T-Lymphocytes, Regulatory - drug effects ; T-Lymphocytes, Regulatory - immunology ; T-Lymphocytes, Regulatory - pathology</subject><ispartof>Journal of neuroimmunology, 2011-04, Vol.233 (1), p.112-119</ispartof><rights>Elsevier B.V.</rights><rights>2010 Elsevier B.V.</rights><rights>Copyright © 2010 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c422t-2c969a74342f9881934fd3f8b5a19c73206aaa612f13070b913e0d86b24571363</citedby><cites>FETCH-LOGICAL-c422t-2c969a74342f9881934fd3f8b5a19c73206aaa612f13070b913e0d86b24571363</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0165572810005333$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21237519$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hashiba, Naomi</creatorcontrib><creatorcontrib>Nagayama, Shigemi</creatorcontrib><creatorcontrib>Araya, Shin-ich</creatorcontrib><creatorcontrib>Inada, Hiroyuki</creatorcontrib><creatorcontrib>Sonobe, Yoshifumi</creatorcontrib><creatorcontrib>Suzumura, Akio</creatorcontrib><creatorcontrib>Matsui, Makoto</creatorcontrib><title>Phenytoin at optimum doses ameliorates experimental autoimmune encephalomyelitis via modulation of immunoregulatory cells</title><title>Journal of neuroimmunology</title><addtitle>J Neuroimmunol</addtitle><description>Abstract We investigated the optimum doses of phenytoin for treatment of myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (EAE). Oral and intraperitoneal administrations of 0.25 to 1.0 mg per mouse (12.5–50 mg/kg) 3 times a week improved the clinical course. Intraperitoneal injections of 1.0 mg phenytoin were the most effective, as a significant reduction in EAE severity was seen after only 2 administrations with that protocol. Treatment efficacy was associated with amelioration of cellular infiltrates in the CNS, and an increase in CD4+ Foxp3+ and CD4+ CD25+ CD127− regulatory T cells as well as CD8+ suppressor/cytotoxic T cells in blood.</description><subject>Allergy and Immunology</subject><subject>Animals</subject><subject>Anticonvulsants - therapeutic use</subject><subject>CD127</subject><subject>CD8</subject><subject>Disease Models, Animal</subject><subject>EAE</subject><subject>Encephalomyelitis, Autoimmune, Experimental - drug therapy</subject><subject>Encephalomyelitis, Autoimmune, Experimental - immunology</subject><subject>Encephalomyelitis, Autoimmune, Experimental - pathology</subject><subject>Immunologic Factors - therapeutic use</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Neurology</subject><subject>Phenytoin</subject><subject>Phenytoin - therapeutic use</subject><subject>Regulatory T cells</subject><subject>T-Lymphocytes, Regulatory - drug effects</subject><subject>T-Lymphocytes, Regulatory - immunology</subject><subject>T-Lymphocytes, Regulatory - pathology</subject><issn>0165-5728</issn><issn>1872-8421</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1v1DAQQC0EotvCX6h847Rbj504yQWBqvIhVQIJOFteZ0IdYjvYTkX-PQ7bcuCCL7ZGb2Y8bwi5BHYABvJqPIwelxisO3C2BfmBMfmE7KBt-L6tODwluwLW-7rh7Rk5T2lkDGpRdc_JGQcumhq6HVk_36Ffc7Ce6kzDnK1bHO1DwkS1w8mGqHN5468Zo3Xos56oXkqCc4tHit7gfKen4NYCZ5vovdXUhX6ZdLbB0zDQP2iI-H2LhbhSg9OUXpBng54Svny4L8i3dzdfrz_sbz-9_3j99nZvKs7znptOdrqpRMWHrm2hE9XQi6E91ho60wjOpNZaAh9AsIYdOxDI-lYeeVU3IKS4IK9OdecYfi6YsnI2bT_QHsOSVCuhbmXDu0LKE2liSCnioOYyso6rAqY262pUj9bVZl0BV8V6Sbx8aLEcHfZ_0x41F-DNCcAy6L3FqJKxm7reRjRZ9cH-v8frf0qYyXpr9PQDV0xjWKIvGhWoVBLUl2332-qBMVaLcn4Dstauwg</recordid><startdate>20110401</startdate><enddate>20110401</enddate><creator>Hashiba, Naomi</creator><creator>Nagayama, Shigemi</creator><creator>Araya, Shin-ich</creator><creator>Inada, Hiroyuki</creator><creator>Sonobe, Yoshifumi</creator><creator>Suzumura, Akio</creator><creator>Matsui, Makoto</creator><general>Elsevier B.V</general><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>20110401</creationdate><title>Phenytoin at optimum doses ameliorates experimental autoimmune encephalomyelitis via modulation of immunoregulatory cells</title><author>Hashiba, Naomi ; Nagayama, Shigemi ; Araya, Shin-ich ; Inada, Hiroyuki ; Sonobe, Yoshifumi ; Suzumura, Akio ; Matsui, Makoto</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c422t-2c969a74342f9881934fd3f8b5a19c73206aaa612f13070b913e0d86b24571363</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Allergy and Immunology</topic><topic>Animals</topic><topic>Anticonvulsants - therapeutic use</topic><topic>CD127</topic><topic>CD8</topic><topic>Disease Models, Animal</topic><topic>EAE</topic><topic>Encephalomyelitis, Autoimmune, Experimental - drug therapy</topic><topic>Encephalomyelitis, Autoimmune, Experimental - immunology</topic><topic>Encephalomyelitis, Autoimmune, Experimental - pathology</topic><topic>Immunologic Factors - therapeutic use</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Neurology</topic><topic>Phenytoin</topic><topic>Phenytoin - therapeutic use</topic><topic>Regulatory T cells</topic><topic>T-Lymphocytes, Regulatory - drug effects</topic><topic>T-Lymphocytes, Regulatory - immunology</topic><topic>T-Lymphocytes, Regulatory - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hashiba, Naomi</creatorcontrib><creatorcontrib>Nagayama, Shigemi</creatorcontrib><creatorcontrib>Araya, Shin-ich</creatorcontrib><creatorcontrib>Inada, Hiroyuki</creatorcontrib><creatorcontrib>Sonobe, Yoshifumi</creatorcontrib><creatorcontrib>Suzumura, Akio</creatorcontrib><creatorcontrib>Matsui, Makoto</creatorcontrib><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 neuroimmunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hashiba, Naomi</au><au>Nagayama, Shigemi</au><au>Araya, Shin-ich</au><au>Inada, Hiroyuki</au><au>Sonobe, Yoshifumi</au><au>Suzumura, Akio</au><au>Matsui, Makoto</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Phenytoin at optimum doses ameliorates experimental autoimmune encephalomyelitis via modulation of immunoregulatory cells</atitle><jtitle>Journal of neuroimmunology</jtitle><addtitle>J Neuroimmunol</addtitle><date>2011-04-01</date><risdate>2011</risdate><volume>233</volume><issue>1</issue><spage>112</spage><epage>119</epage><pages>112-119</pages><issn>0165-5728</issn><eissn>1872-8421</eissn><abstract>Abstract We investigated the optimum doses of phenytoin for treatment of myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (EAE). Oral and intraperitoneal administrations of 0.25 to 1.0 mg per mouse (12.5–50 mg/kg) 3 times a week improved the clinical course. Intraperitoneal injections of 1.0 mg phenytoin were the most effective, as a significant reduction in EAE severity was seen after only 2 administrations with that protocol. Treatment efficacy was associated with amelioration of cellular infiltrates in the CNS, and an increase in CD4+ Foxp3+ and CD4+ CD25+ CD127− regulatory T cells as well as CD8+ suppressor/cytotoxic T cells in blood.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>21237519</pmid><doi>10.1016/j.jneuroim.2010.12.006</doi><tpages>8</tpages></addata></record> |
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| subjects | Allergy and Immunology Animals Anticonvulsants - therapeutic use CD127 CD8 Disease Models, Animal EAE Encephalomyelitis, Autoimmune, Experimental - drug therapy Encephalomyelitis, Autoimmune, Experimental - immunology Encephalomyelitis, Autoimmune, Experimental - pathology Immunologic Factors - therapeutic use Mice Mice, Inbred C57BL Neurology Phenytoin Phenytoin - therapeutic use Regulatory T cells T-Lymphocytes, Regulatory - drug effects T-Lymphocytes, Regulatory - immunology T-Lymphocytes, Regulatory - pathology |
| title | Phenytoin at optimum doses ameliorates experimental autoimmune encephalomyelitis via modulation of immunoregulatory cells |
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