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Fingolimod attenuates experimental autoimmune neuritis and contributes to Schwann cell-mediated axonal protection
BACKGROUND: Fingolimod, a sphingosine-1-phosphate receptor modulator with well-described immunomodulatory properties involving peripheral immune cell trafficking, was the first oral agent approved for the treatment of relapsing remitting multiple sclerosis. Analogous immunomodulatory treatment optio...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5406994/ https://www.ncbi.nlm.nih.gov/pubmed/28446186 http://dx.doi.org/10.1186/s12974-017-0864-z |
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author | Ambrosius, Björn Pitarokoili, Kalliopi Schrewe, Lisa Pedreiturria, Xiomara Motte, Jeremias Gold, Ralf |
author_facet | Ambrosius, Björn Pitarokoili, Kalliopi Schrewe, Lisa Pedreiturria, Xiomara Motte, Jeremias Gold, Ralf |
author_sort | Ambrosius, Björn |
collection | PubMed |
description | BACKGROUND: Fingolimod, a sphingosine-1-phosphate receptor modulator with well-described immunomodulatory properties involving peripheral immune cell trafficking, was the first oral agent approved for the treatment of relapsing remitting multiple sclerosis. Analogous immunomodulatory treatment options for chronic peripheral autoimmune neuropathies are lacking. METHODS: We tested fingolimod in the animal model of experimental autoimmune neuritis in Lewis rat. Six to eight-week-old female rats were immunized with P2 peptide and from this day on treated with fingolimod. Histology of the sciatic nerve was done to analyze T cell and macrophage cell count, intercellular adhesion molecule (ICAM) and amyloid precursor protein (APP) expression, as well as apoptotic Schwann cell counts. RESULTS: Preventive oral treatment with 0.1 mg/kg up to 3 mg/kg fingolimod once daily dissolved in rapeseed oil completely ameliorated clinical neuritis signs. It reduced circulating peripheral blood T cells and infiltrating T cells and macrophages in the sciatic nerve, whereas at the same time, it preserved blood-nerve barrier impermeability. Most importantly, fingolimod showed beneficial properties on the pathogenic process as indicated by fewer apoptotic Schwann cells and a lower amount of amyloid precursor protein indicative of axonal damage at the peak of disease course. CONCLUSIONS: Taken together, orally administered low-dose fingolimod showed an impressive immunomodulatory effect in the rat model of experimental autoimmune neuritis. Our current observations introduce fingolimod as an attractive treatment option for neuritis patients. |
format | Online Article Text |
id | pubmed-5406994 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-54069942017-05-02 Fingolimod attenuates experimental autoimmune neuritis and contributes to Schwann cell-mediated axonal protection Ambrosius, Björn Pitarokoili, Kalliopi Schrewe, Lisa Pedreiturria, Xiomara Motte, Jeremias Gold, Ralf J Neuroinflammation Research BACKGROUND: Fingolimod, a sphingosine-1-phosphate receptor modulator with well-described immunomodulatory properties involving peripheral immune cell trafficking, was the first oral agent approved for the treatment of relapsing remitting multiple sclerosis. Analogous immunomodulatory treatment options for chronic peripheral autoimmune neuropathies are lacking. METHODS: We tested fingolimod in the animal model of experimental autoimmune neuritis in Lewis rat. Six to eight-week-old female rats were immunized with P2 peptide and from this day on treated with fingolimod. Histology of the sciatic nerve was done to analyze T cell and macrophage cell count, intercellular adhesion molecule (ICAM) and amyloid precursor protein (APP) expression, as well as apoptotic Schwann cell counts. RESULTS: Preventive oral treatment with 0.1 mg/kg up to 3 mg/kg fingolimod once daily dissolved in rapeseed oil completely ameliorated clinical neuritis signs. It reduced circulating peripheral blood T cells and infiltrating T cells and macrophages in the sciatic nerve, whereas at the same time, it preserved blood-nerve barrier impermeability. Most importantly, fingolimod showed beneficial properties on the pathogenic process as indicated by fewer apoptotic Schwann cells and a lower amount of amyloid precursor protein indicative of axonal damage at the peak of disease course. CONCLUSIONS: Taken together, orally administered low-dose fingolimod showed an impressive immunomodulatory effect in the rat model of experimental autoimmune neuritis. Our current observations introduce fingolimod as an attractive treatment option for neuritis patients. BioMed Central 2017-04-26 /pmc/articles/PMC5406994/ /pubmed/28446186 http://dx.doi.org/10.1186/s12974-017-0864-z Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Ambrosius, Björn Pitarokoili, Kalliopi Schrewe, Lisa Pedreiturria, Xiomara Motte, Jeremias Gold, Ralf Fingolimod attenuates experimental autoimmune neuritis and contributes to Schwann cell-mediated axonal protection |
title | Fingolimod attenuates experimental autoimmune neuritis and contributes to Schwann cell-mediated axonal protection |
title_full | Fingolimod attenuates experimental autoimmune neuritis and contributes to Schwann cell-mediated axonal protection |
title_fullStr | Fingolimod attenuates experimental autoimmune neuritis and contributes to Schwann cell-mediated axonal protection |
title_full_unstemmed | Fingolimod attenuates experimental autoimmune neuritis and contributes to Schwann cell-mediated axonal protection |
title_short | Fingolimod attenuates experimental autoimmune neuritis and contributes to Schwann cell-mediated axonal protection |
title_sort | fingolimod attenuates experimental autoimmune neuritis and contributes to schwann cell-mediated axonal protection |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5406994/ https://www.ncbi.nlm.nih.gov/pubmed/28446186 http://dx.doi.org/10.1186/s12974-017-0864-z |
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