Tumor Necrosis Factor-induced Decrease of Cochlear Blood Flow Can Be Reversed by Etanercept or JTE-013

Sharaf, Kariem; Ihler, Friedrich; Bertlich, Mattis; Reichel, Christoph A.; Berghaus, Alexander und Canis, Martin (2016): Tumor Necrosis Factor-induced Decrease of Cochlear Blood Flow Can Be Reversed by Etanercept or JTE-013. In: Otology & Neurotology, Bd. 37, Nr. 7, E203-E208

Abstract

Hypothesis: This study aimed to quantify the effects of tumor necrosis factor (TNF) inhibitor Etanercept and sphin-gosine-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 (1.0mg/ml), JTE-013 (10mmol/L), or vehicle (0.9 % NaCl solution or ethanol: phosphate-buffered saline buffer, respectively). Results: After decreasing CBF with TNF (p<0.001, twoway 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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1531-7129
• Sprache: Englisch