Ambrosius, Björn; Pitarokoili, Kalliopi; Schrewe, Lisa; Pedreiturria, Xiomara; Motte, Jeremias; Gold, Ralf (2017). Fingolimod attenuates experimental autoimmune neuritis and contributes to Schwann cell-mediated axonal protection. Journal of neuroinflammation, 14(1), p. 92. BioMed Central 10.1186/s12974-017-0864-z
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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.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Neurology |
UniBE Contributor: |
Thiele, Lisa |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
1742-2094 |
Publisher: |
BioMed Central |
Language: |
English |
Submitter: |
Stefanie Hetzenecker |
Date Deposited: |
27 Feb 2018 10:38 |
Last Modified: |
02 Mar 2023 23:29 |
Publisher DOI: |
10.1186/s12974-017-0864-z |
PubMed ID: |
28446186 |
Uncontrolled Keywords: |
Chronic inflammatory demyelinating neuropathy (CIDP) Guillain-Barré syndrome (GBS) Myelin Nerve conduction studies Nerve excitability |
BORIS DOI: |
10.7892/boris.107967 |
URI: |
https://boris.unibe.ch/id/eprint/107967 |
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