Inflammation Potentiates Cochlear Uptake of Ototoxins and Drug-Induced Hearing Loss
Serious bacterial infections are often treated with aminoglycosides, especially when the cause of systemic infection is unknown. Severe infections trigger specific systemic inflammatory response pathways. Aminoglycosides are primarily trafficked across the cochlear blood-labyrinth barrier into the stria vascularis, prior to clearance into endolymph and entry into hair cells with subsequent cytotoxicity and loss of auditory function: cochleotoxicity. Systemic inflammation potentiates cochlear uptake of aminoglycosides and increases the risk of hearing loss in both preclinical models and human studies. Here, we review the data that establishes the above narrative, and articulate the need for translational studies to promote ototoxicity monitoring in neonatal intensive care units and cystic fibrosis clinics.
KeywordsAminoglycosides Ototoxicity Stria vascularis Drug trafficking Infection
Figures drafted by Karen Thiebes, of Simplified Science Publishing, LLC. I thank lab members for discussion on the manuscript. This research was supported by R01 awards (DC004555, DC12588) from the National Institute of Deafness and Other Communication Disorders. The content is solely the responsibility of the author and does not represent the official views of the NIH, Oregon Health & Science University or the VA Portland Health Care System. The author declares no existing or potential conflict of interest.
This work was supported by NIDCD R01 awards DC04555 and DC012588.
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