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 (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

[img]
Preview
Text
document.pdf - Published Version
Available under License Creative Commons: Attribution (CC-BY).

Download (1MB) | Preview

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)

Division/Institute:

04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Neurology

UniBE Contributor:

Schrewe, 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:

22 Oct 2019 19:42

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

Actions (login required)

Edit item Edit item
Provide Feedback