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

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.

• Authors: Kariem Sharaf, Friedrich Ihler, Mattis Bertlich, Christoph A Reichel, Alexander Berghaus, Martin Canis
• Journal: Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology (Otol Neurotol) Vol. 37 Issue 7 Pg. e203-8 (08 2016) ISSN: 1537-4505 [Electronic] United States
• PMID: 27295443 (Publication Type: Journal Article)

Chemical References

• Immunosuppressive Agents
• JTE 013
• Pyrazoles
• Pyridines
• Tumor Necrosis Factor-alpha
• Etanercept

Topics

• Animals
• Cochlea (blood supply, drug effects, metabolism)
• Disease Models, Animal
• Etanercept (pharmacology)
• Guinea Pigs
• Hearing Loss, Sensorineural (etiology, metabolism)
• Immunosuppressive Agents (pharmacology)
• Microcirculation (drug effects)
• Pyrazoles (pharmacology)
• Pyridines (pharmacology)
• Random Allocation
• Tumor Necrosis Factor-alpha (antagonists & inhibitors)