Intratympanic Lipopolysaccharide Elevates Systemic Fluorescent Gentamicin Uptake in the Cochlea

Area of Science:

• Otolaryngology
• Immunology
• Pharmacology

Background:

• Lipopolysaccharide (LPS) is a bacterial endotoxin that triggers inflammatory responses.
• Acute otitis media (AOM) induced by LPS causes inner ear changes.
• Understanding gentamicin uptake in AOM is crucial for managing ototoxicity.

Purpose of the Study:

• To establish an AOM mouse model using LPS.
• To investigate gentamicin uptake in the inner ear during AOM.
• To elucidate the role of cochlear inflammation in AOM-related ototoxicity.

Main Methods:

• An AOM mouse model was created using intratympanic LPS injection.
• Fluorescently tagged gentamicin (GTTR) was administered systemically.
• Macrophage activity and inner ear cytokine profiles were analyzed.

Main Results:

• LPS-induced AOM led to conductive hearing loss and elevated hearing thresholds.
• Cochlear inflammation, including macrophage infiltration and cytokine up-regulation, was observed.
• Gentamicin uptake in the stria vascularis and sensory hair cells significantly increased in AOM ears.

Conclusions:

• The pathological cochlea is more susceptible to ototoxic drugs like aminoglycosides.
• Clinical concerns regarding aminoglycoside ototoxicity in AOM treatment are justified.
• Cochlear inflammation plays a key role in enhanced ototoxic drug uptake.