Abstract Details

Title Effects of Fingolimod on Cytokine and Chemokine Levels in Patients with Multiple Sclerosis

Topic Multiple Sclerosis

Presentation(s) P4 - Poster Session 4 (5:30 PM-6:30 PM)

Poster/Presentation
Number 15-048

Objective

In this study, we investigated the effects of fingolimod on peripheral cytokine/chemokine levels and lymphocyte subtypes.

Background

Fingolimod inhibits the egress of lymphocytes to the systemic circulation by inhibition of the sphingosine 1 phosphate receptor. Although the reduction of circulating auto-reactive lymphocyte counts is believed to play a role, fingolimod’s exact mechanism of action in relapsing-remitting multiple sclerosis (RRMS) is still unknown.

Design/Methods This study was a 6-month, multicenter, prospective, interventional, single arm, open-label study. Patients with RRMS were treated with fingolimod 0.5 mg/day. Peripheral blood samples were taken from 80 healthy controls and 60 patients at baseline (visit 1), third (visit 2), and sixth months (visit 3). Serum cytokine levels were measured by multiplex immunoassay. Peripheral blood immunophenotyping and intracellular cytokine assessment were done by flow cytometry.

Results Patients' serum levels of CXCL13, IL-23, IL-4, IL-6, VLA-4, CXCL10, TNF-alpha, IL-13 and IL-22 were similar to healthy controls, whereas IL-17 levels were significantly lower. The levels of neutrophil-recruiting chemokines MCP-1 (p<0.001) and CCL5 (p=0.001) were increased. Although the CD3+ (p <0.001) and CD4+ (p <0.001) lymphocyte ratios were decreased, the most significant decrease was observed in the ratio of CD19+ lymphocytes (p<0.001). Interestingly, fingolimod increased the ratios of CD8+ T cells (p<0.001), CD16+CD56+ NK cells (p <0.001) and CD4+CD25hi regulatory T cells (Treg) (p <0.001). Ratios of anti-inflammatory IL-4 (p<0.001) and IL-10 (p=0.012) producing Tregs were also increased.

Conclusions Fingolimod treatment mainly reduces CD4+ helper T lymphocytes and B cells but not CD8+ T cells and NK cells. Thus, it acts primarily by interfering with the antigen presentation without significantly affecting cytotoxic immune cells that are involved in innate immune responses. Moreover, fingolimod treatment does not explicitly affect Th1/Th17-type immune responses but enhances the production of anti-inflammatory Treg populations.

Authors/Disclosures
Murat Kurtuncu, MD (Istanbul University) PRESENTER	Dr. Kurtuncu has nothing to disclose.
	No disclosure on file
	No disclosure on file
Recai Turkoglu	Recai Turkoglu has nothing to disclose.
Burcu Altunrende, MD (Istanbul Bilim University - Dept of Neurology)	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Mithat Kasap	No disclosure on file
Zeynep Caliskan	No disclosure on file
	No disclosure on file
Mefkure Eraksoy, MD (ISTANBUL UNIVERSITY)	Dr. Eraksoy has nothing to disclose.
Erdem Tuzun	Erdem Tuzun has nothing to disclose.

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