Effects of Fingolimod on Cytokine and Chemokine Levels in Patients with Multiple Sclerosis (P4.2-048)

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 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. Disclosure: Dr. Kurtuncu has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Merck, Novartis Pharmaceuticals, Teva, Sanofi Genzyme, Bayer, and Roche. Dr. Yilmaz has nothing to disclose. Dr. Akcay has nothing to disclose. Dr. Turkoglu has nothing to disclose. Dr. Altunrende has nothing to disclose. Dr. Ulusoy has nothing to disclose. Dr. Adin Cinar has nothing to disclose. Dr. Icoz has nothing to disclose. Dr. Kasap has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Novartis. Dr. Caliskan has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Novartis. Dr. Otunc has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Novartis. Dr. Eraksoy has nothing to disclose. Dr. Tuzun has nothing to disclose.