Inflammation potentiates cochlear uptake of ototoxins and drug-induced hearing loss

Abstract

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.