About: FTY720 (fingolimod) modulates the severity of viral-induced encephalomyelitis and demyelination

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About: FTY720 (fingolimod) modulates the severity of viral-induced encephalomyelitis and demyelination Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : covidontheweb.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	FTY720 (fingolimod) modulates the severity of viral-induced encephalomyelitis and demyelination
Creator	Rosen, Hugh Blanc, Caroline Lane, Thomas
Source	PMC
abstract	BACKGROUND: FTY720 (fingolimod) is the first oral drug approved by the Food and Drug Administration for treatment of patients with the relapsing-remitting form of the human demyelinating disease multiple sclerosis. Evidence suggests that the therapeutic benefit of FTY720 occurs by preventing the egress of lymphocytes from lymph nodes thereby inhibiting the infiltration of disease-causing lymphocytes into the central nervous system (CNS). We hypothesized that FTY720 treatment would affect lymphocyte migration to the CNS and influence disease severity in a mouse model of viral-induced neurologic disease. METHODS: Mice were infected intracranially with the neurotropic JHM strain of mouse hepatitis virus. Infected animals were treated with increasing doses (1, 3 and 10 mg/kg) of FTY720 and morbidity and mortality recorded. Infiltration of inflammatory virus-specific T cells (tetramer staining) into the CNS of FTY720-treated mice was determined using flow cytometry. The effects of FTY720 treatment on virus-specific T cell proliferation, cytokine production and cytolytic activity were also determined. The severity of neuroinflammation and demyelination in FTY720-treated mice was examined by flow cytometry and histopathologically, respectively, in the spinal cords of the mice. RESULTS: Administration of FTY720 to JHMV-infected mice resulted in increased clinical disease severity and mortality. These results correlated with impaired ability to control viral replication (P < 0.05) within the CNS at days 7 and 14 post-infection, which was associated with diminished accumulation of virus-specific CD4+ and CD8+ T cells (P < 0.05) into the CNS. Reduced neuroinflammation in FTY720-treated mice correlated with increased retention of T lymphocytes within draining cervical lymph nodes (P < 0.05). Treatment with FTY720 did not affect virus-specific T cell proliferation, expression of IFN-γ, TNF-α or cytolytic activity. FTY720-treated mice exhibited a reduction in the severity of demyelination associated with dampened neuroinflammation. CONCLUSION: These findings indicate that FTY720 mutes effective anti-viral immune responses through impacting migration and accumulation of virus-specific T cells within the CNS during acute viral-induced encephalomyelitis. FTY720 treatment reduces the severity of neuroinflammatory-mediated demyelination by restricting the access of disease-causing lymphocytes into the CNS but is not associated with viral recrudescence in this model.
has issue date	2014-08-20(xsd:dateTime)
bibo:doi	10.1186/s12974-014-0138-y
bibo:pmid	25138356
has license	cc-by
sha1sum (hex)	b147a9e7654ef4257a7c45cae6606543a7864c80
schema:url	https://doi.org/10.1186/s12974-014-0138-y
resource representing a document's title	FTY720 (fingolimod) modulates the severity of viral-induced encephalomyelitis and demyelination
has PubMed Central identifier	PMC4148542
has PubMed identifier	25138356
schema:publication	J Neuroinflammation
resource representing a document's body	covid:b147a9e7654ef4257a7c45cae6606543a7864c80#body_text
is schema:about of	named entity 'SEVERITY' named entity 'fingolimod' named entity 'mouse' named entity 'LYMPHOCYTES' named entity 'INFLUENCE' named entity 'BENEFIT' named entity 'REMITTING' named entity 'MOUSE MODEL' named entity 'CAUSING' named entity 'DEMYELINATING DISEASE' named entity 'LYMPHOCYTE MIGRATION' named entity 'CNS' named entity 'MODEL OF' named entity 'DISEASE' named entity 'INDUCED' named entity 'DRUG' named entity 'INFILTRATION' named entity 'EVIDENCE' named entity 'PATIENTS' named entity 'VIRAL-' named entity 'MULTIPLE SCLEROSIS' named entity 'INDUCED' named entity 'A MOUSE' named entity 'APPROVED BY' named entity 'FORM' named entity 'BACKGROUND' named entity 'FTY720' named entity 'DEMYELINATION' named entity 'THERAPEUTIC' named entity 'TREATMENT' named entity 'AFFECT' named entity 'NEUROLOGIC DISEASE' named entity 'DISEASE SEVERITY' named entity 'VIRAL-' named entity 'ENCEPHALOMYELITIS' named entity 'ORAL' named entity 'CENTRAL NERVOUS SYSTEM' named entity 'HUMAN' named entity 'LYMPH NODES' named entity 'FOOD AND DRUG ADMINISTRATION' named entity 'PREVENTING' named entity 'INHIBITING' named entity 'FTY720' named entity 'RELAPSING' covid:arg/b147a9e7654ef4257a7c45cae6606543a7864c80 named entity 'hypothesized' named entity 'central nervous system (CNS)' named entity 'Drug' named entity 'lymph nodes' named entity 'FTY720' named entity 'CNS' named entity 'lymph nodes' named entity 'FTY720' named entity 'FTY720' named entity 'fingolimod' named entity 'CNS' named entity 'FTY720' named entity 'therapeutic benefit' named entity 'lymphocyte' named entity 'FTY720' named entity 'epitope' named entity 'CNS' named entity 'CD4' named entity 'sphingosine-1-phosphate' named entity 'FTY720' named entity 'knock-in' named entity 'cytotoxic T lymphocytes' named entity 'CD8' named entity 'staining' named entity 'mice' named entity 'conjugated' named entity 'white matter tracts' named entity 'lymphocytic choriomeningitis' named entity 'FTY720' named entity 'clinical studies' named entity 'mice' named entity 'cytolytic activity' named entity 'cytokine' named entity 'Gilenya'

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