Abstract Details

Title Fingolimod Induced Cytokine Profile in Cultured Monocytes from Multiple Sclerosis Patients

Topic MS and Related Diseases

Presentation(s) P05 - (-)

Poster/Presentation
Number 155

Objective

Background BACKGROUND: Fingolimod is a sphingosine-1-phosphate receptor (S1PR) agonist approved for the treatment of RRMS patients. In addition to its effect on lymphocyte migration, Fingolimod is known to affect cytokine production in immune cells; however, the exact cytokine changes induced by Fingolimod and their functional role in MS are unclear.

Design/Methods DESIGN/METHODS: Peripheral blood mononuclear cells (PBMC) from 30 RRMS patients, 23 females, age 37.6±1.3 years, disease duration 8.8±1.4 years, EDSS 1.6±0.2 were incubated at 37[ordm]C with or without 2.5ng/ml Fingolimod for 24 hours and thereafter supernatants were assayed for the following cytokines: IL-1a(b), IL-2(5)(6)(7)(8)(10)(13)(17A), IL-12(p40)(p70), TNFa(b), IFN-g; chemokines: CCL2(3)(4)(5)(7)(11), CXCL1(8)(10); and growth factors: FGF-b, G-CSF, GM-CSF, PDGF-BB, VEGF-A and NFF-b, using multiplexed arrays based on Luminex X-map technology. Expression data was analyzed by paired T-test. The significantly changed cytokines with p<0.05 after Bonferroni correction for multiple comparisons, were subjected to functional regulatory network analysis by Ingenuity software (www.ingenuity.com).

Results RESULTS: Fingolimod significantly increased the expression of IL-6 (p=0.03), IL10 (2.1*10-3) and IL17A (p=0.8*10-3) cytokines, CXCL1 (p=3.3*10-5) chemokine and FGFb (p=0.3*10-3) growth factor. This profile suggests a new humoral mediated neuroprotective mechanism induced by Fingolimod in MS. Accordingly, cytokines activated by Fingolimod, either directly or indirectly, could promote neuronal regeneration and remyelination (IL6, IL10 and IL17A), enhance neuronal survival (FGFb) and activate neuronal progenitor cells (CXCL1).

Conclusions CONCLUSIONS: In-vitro induction of cytokine-chemokine-growth factor profile by Fingolimod in MS suggests the possibility of neuroprotective mechanism. This mechanism is distinct from lymphocyte trafficking machinery or direct S1PR-mediated neuroprotection.

Authors/Disclosures
Anat Achiron, MD, PhD, FAAN (Sheba Medical Center, Tel-Hashomer) PRESENTER	Dr. Achiron has nothing to disclose.
	No disclosure on file
Mark Dolev Dolgopiat, MD	No disclosure on file
David Magalashvili, MD	No disclosure on file
Michael Gurevich (Sheba Medical Center)	No disclosure on file
Daniel O. Claassen, MD, FAAN (Vanderbilt University Medical Center)	Dr. Claassen has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Alterity. Dr. Claassen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lundbeck. Dr. Claassen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Teva. Dr. Claassen has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for AskBio. Dr. Claassen has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for University of Michigan. Dr. Claassen has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Cognition Therapeutics . Dr. Claassen has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Amylyx. The institution of Dr. Claassen has received research support from NIH. The institution of Dr. Claassen has received research support from CHDI. The institution of Dr. Claassen has received research support from HDSA. The institution of Dr. Claassen has received research support from Department of Defense. The institution of Dr. Claassen has received research support from CHDI.

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