Tumor Necrosis Factor-induced Decrease of Cochlear Blood Flow Can Be Reversed by Etanercept or JTE-013. Issue 7 (August 2016)

• Record Type: Journal Article
• Authors: Sharaf, Kariem; Ihler, Friedrich; Bertlich, Mattis; Reichel, Christoph A.; Berghaus, Alexander; Canis, Martin
• Is Part Of: Otology & neurotology. Volume 37:Issue 7(2016)
• Page Start: e203
• Page End: e208
• Publication Date: 2016-08
• Subjects: Etanercept -- Fluorescence microscopy -- Guinea pig -- JTE-013 -- Sphingosine-1-phosphate -- Stria vascularis -- Sudden sensorineural hearing loss -- TNF; Otology -- Periodicals; Ear -- Diseases -- Periodicals; Skull base -- Surgery -- Periodicals; 617.8005
• DOI: 10.1097/MAO.0000000000001095
• Languages: English
• ISSNs: 1531-7129

Abstract

Abstract : Hypothesis: This study aimed to quantify the effects of tumor necrosis factor (TNF) inhibitor Etanercept and sphingosine-1-phosphate receptor 2 antagonist JTE-013 on cochlear blood flow in guinea pigs after TNF-induced decrease. Background: Sudden sensorineural hearing loss is a common cause for disability and reduced quality of life. Good understanding of the pathophysiology and strong evidence-based therapy concepts are still missing. In various inner ear disorders, inflammation and impairment of cochlear blood flow (CBF) have been considered factors in the pathophysiology. A central mediator of inflammation and microcirculation in the cochlea is TNF. S1P acts downstream in one TNF pathway. Methods: Cochlea lateral wall vessels were exposed surgically and assessed by intravital microscopy in guinea pigs in vivo. Twenty-eight animals were randomly distributed into four groups of seven each. Exposed vessels were superfused by TNF (5.0 ng/ml) and afterward repeatedly either by Etanercept (1.0 μg/ml), JTE-013 (10 μmol/L), or vehicle (0.9 % NaCl solution or ethanol: phosphate-buffered saline buffer, respectively). Results: After decreasing CBF with TNF ( p <0.001, two-way RM ANOVA), both treatments reversed CBF, compared with vehicle ( p <0.001, two-way RM ANOVA). The comparison of the vehicle groups showed no difference ( p = 0.969, two-way RM ANOVA), while there was also no difference between the treatment groups ( p = 0.850, two-way RM ANOVA). Conclusion: Both Etanercept and JTE-013 reverse the decreasing effect of TNF on cochlear blood flow and, therefore, TNF and the S1P-signalling pathway might be targets for treatment of microcirculation-related hearing loss.