title: Interferon-Beta Increases Plasma Ceramides of Specific Chain Length in Multiple Sclerosis Patients, Unlike Fingolimod or Natalizumab.
abstract: Fingolimod is used for the treatment of multiple sclerosis (MS) and targets receptors for the bioactive sphingolipid sphingosine-1-phosphate (S1P). Whether fingolimod or other MS therapies conversely affect plasma concentrations of sphingolipids has, however, not yet been analyzed. Herein, we quantified 15 representative sphingolipid species by mass spectrometry in plasma from relapsing-remitting MS patients currently under fingolimod (n= 24), natalizumab (n= 16), or IFN-β (n= 18) treatment. Healthy controls (n= 21) and untreated MS patients (n= 11) served as control groups. IFN-ß treatment strongly increased plasma level of C16:0, C18:0, C20:0, and C24:1ceramides compared to healthy controls, untreated patients, or patients receiving fingolimod or natalizumab medication. Natalizumab treatment increased plasma concentrations of both S1P and sphinganine-1-phosphate, whereas fingolimod treatment did not affect any of these lipids. Correlations of sphingolipids with the Expanded Disability Status Scale and other disease specific parameters revealed no systemic change of sphingolipids in MS, independent of the respective treatment regime. These results indicate type I interferon treatment to cause a strong and specific increase in ceramide level. If confirmed in larger cohorts, these data have implications for the efficacy and adverse effects of IFN-β. Moreover, quantification of ceramides soon after therapy initiation may help to identify therapy-responsive patients.
authors.affiliation: Pharmazentrum Frankfurt, Institute of Pharmacology and Toxicology, Goethe University Frankfurt Frankfurt am Main, Germany.
authors.forename: Florian M
authors.initials: FM
authors.lastname: Ottenlinger
authors.affiliation: Center for Neurology and Neurosurgery, Goethe University Frankfurt Frankfurt am Main, Germany.
authors.forename: Christoph A
authors.initials: CA
authors.lastname: Mayer
authors.affiliation: Pharmazentrum Frankfurt/ZAFES, Institute for Clinical Pharmacology, Goethe University Frankfurt Frankfurt am Main, Germany.
authors.forename: Nerea
authors.initials: N
authors.lastname: Ferreirós
authors.affiliation: Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Project Group TMP, Goethe University Frankfurt Frankfurt am Main, Germany.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Schreiber
authors.affiliation: Pharmazentrum Frankfurt, Institute of Pharmacology and Toxicology, Goethe University Frankfurt Frankfurt am Main, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Schwiebs
authors.affiliation: Pharmazentrum Frankfurt, Institute of Pharmacology and Toxicology, Goethe University Frankfurt Frankfurt am Main, Germany.
authors.forename: Katrin G
authors.initials: KG
authors.lastname: Schmidt
authors.affiliation: Institute for Biostatistics and Mathematical Modelling, Goethe University Frankfurt Frankfurt am Main, Germany.
authors.forename: Hanns
authors.initials: H
authors.lastname: Ackermann
authors.affiliation: Pharmazentrum Frankfurt, Institute of Pharmacology and Toxicology, Goethe University Frankfurt Frankfurt am Main, Germany.
authors.forename: Josef M
authors.initials: JM
authors.lastname: Pfeilschifter
authors.affiliation: Pharmazentrum Frankfurt, Institute of Pharmacology and Toxicology, Goethe University Frankfurt Frankfurt am Main, Germany.
authors.forename: Heinfried H
authors.initials: HH
authors.lastname: Radeke
keywords: ceramides; fingolimod; interferon-beta; multiple sclerosis; natalizumab; sphinganines; sphingolipids