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Review
. 2019 Dec;8(2):231-240.
doi: 10.1007/s40120-019-00162-7. Epub 2019 Nov 6.

Fingolimod Immune Effects Beyond Its Sequestration Ability

Francesco Sica  1 , Diego Centonze  2   3 , Fabio Buttari  1
Affiliations
Review

Fingolimod Immune Effects Beyond Its Sequestration Ability

Francesco Sica et al. Neurol Ther. 2019 Dec.

Abstract

Fingolimod is the first orally administered drug approved for the treatment of relapsing-remitting multiple sclerosis (MS). This drug, modulating sphingosine receptors, regulates the trafficking of lymphocytes between primary and secondary lymphoid organs, trapping naïve T cells and central memory T cells in secondary lymphoid organs, without affecting effector memory T cells and therefore without compromising immunosurveillance. Additionally, fingolimod inhibits expression of Th1 and Th17 cytokines and enhances regulatory T-cell differentiation. It also acts on the B arm of immunity through an increased ratio of naïve to memory B cells, higher percentage of plasma cells, and highly increased proportion of transitional B cells as well as additional regulatory subsets. Fingolimod treatment enhances the capacity of regulatory B cells to transmigrate across brain endothelial cells. In fact, patients treated with fingolimod have increased regulatory B-cell frequency in the cerebrospinal fluid. These findings suggest a novel role for fingolimod in MS, by both direct effects and indirect partitioning effects on lymphocytes.

Keywords: B lymphocytes; Fingolimod; Mechanism of action; T lymphocytes.

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Conflict of interest statement

Francesco Sica has served on advisory boards for Merck Serono and has received travel grants from Merck Serono, Teva, Biogen, Sanofi-Genzyme, and Novartis. Diego Centonze is an advisory board member of Almirall, Bayer Schering, Biogen, GW Pharmaceuticals, Merck Serono, Novartis, Roche, Sanofi-Genzyme, and Teva, and has received honoraria for speaking or consultation fees from Almirall, Bayer Schering, Biogen, GW Pharmaceuticals, Merck Serono, Novartis, Roche, Sanofi-Genzyme, and Teva. He is also the principal investigator in clinical trials for Bayer Schering, Biogen, Merck Serono, Mitsubishi, Novartis, Roche, Sanofi-Genzyme, and Teva. His preclinical and clinical research was supported by grants from Bayer Schering, Biogen Idec, Celgene, Merck Serono, Novartis, Roche, Sanofi-Genzyme, and Teva. Fabio Buttari has served on advisory boards for Teva, Biogen, Merck Serono, and Roche, and has received travel grants and/or speaker honoraria from Merck Serono, Teva, Biogen, Sanofi-Genzyme, and Novartis.

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