Fingolimod (FTY-720) is Capable of Reversing Tumor Necrosis Factor Induced Decreases in Cochlear Blood Flow

Bertlich, Mattis; Ihler, Friedrich; Weiss, Bernhard G.; Freytag, Saskia; Jakob, Mark; Strupp, Michael; Pellkofer, Hannah und Canis, Martin (2017): Fingolimod (FTY-720) is Capable of Reversing Tumor Necrosis Factor Induced Decreases in Cochlear Blood Flow. In: Otology & Neurotology, Vol. 38, No. 8: pp. 1213-1216

Abstract

Hypothesis: The potential of Fingolimod (FTY-720), a sphingosine-1-phosphate analogue, to revoke the changes in cochlear blood flow induced by tumor necrosis factor (TNF) was investigated. Background: Impairment of cochlear blood flow has often been considered as the common final pathway of various inner ear pathologies. TNF, an ubiquitous cytokine, plays a major role in these pathologies, reducing cochlear blood flow via sphingosine-1-phosphate-signaling. Methods: Fifteen Dunkin-Hartley guinea pigs were randomly assigned to one of three groups (placebo/placebo, TNF/placebo, TNF/FTY-720). Cochlear microcirculation was quantified over 60 minutes by in vivo fluorescence microscopy before and after topical application of placebo or TNF (5 ng/ml) and after subsequent application of placebo or FTY-720 (200 mu g/ml). Results: Treatment with TNF led to a significant decrease of cochlear blood flow. Following this, application of placebo caused no significant changes while application of FTY-720 caused a significant rise in cochlear blood flow. Conclusions: FTY-720 is capable of reversing changes in cochlear blood flow induced by application of TNF. This makes FTY-720 a valid candidate for potential treatment of numerous inner ear pathologies.

• Item Type: Journal article
• Faculties: Medicine
• Subjects: 600 Technology > 610 Medicine and health
• ISSN: 1531-7129
• Alliance/National Licence: This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.
• Language: English