Intratympanic immunosuppressives for prevention of immune-mediated sensorineural hearing loss.
OBJECTIVE
Round window membrane application of immunosuppressives reduces cochlear inflammation and hearing loss in a guinea pig model of sterile labyrinthitis.


BACKGROUND
Systemic immunosuppressives are used to treat sensorineural hearing loss due to inflammation (autoimmune, bacterial, viral), which in animal models causes hearing loss. Transtympanic application of drugs is an attractive and possibly efficacious method of treatment that avoids systemic toxicities.


METHODS
Sterile labyrinthitis was created using keyhole limpet hemocyanin (KLH). Dexamethasone (0.048 mg/day and 0.288 mg/day), cyclosporine (0.5%), prednisolone acetate (1%), fluorouracil, (5%), and FK506 (0.01%) were delivered to the round window membrane with one injection (filling middle ear space) or osmotic minipumps. Efficacy was evaluated by auditory brainstem response and histology.


RESULTS
No drug was effective at reducing hearing loss or inflammation.


CONCLUSIONS
Local application of immunosuppressives did not suppress inner ear inflammatory infiltrates and hearing loss in KLH-induced labyrinthitis in a guinea pig model.
Division of Otolaryngology, University of California, San Diego, School of Medicine, La Jolla 92093-0666, USA.
G S
GS
Yang
H T
HT
Song
E M
EM
Keithley
J P
JP
Harris
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D016572:Cyclosporine / Q000627:therapeutic use*; D003907:Dexamethasone / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005472:Fluorouracil / Q000627:therapeutic use*; D006168:Guinea Pigs; D006319:Hearing Loss, Sensorineural / Q000175:diagnosis / Q000209:etiology*; D006433:Hemocyanins; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007267:Injections; D007762:Labyrinthitis / Q000150:complications* / Q000276:immunology / Q000517:prevention & control*; D011239:Prednisolone / Q000627:therapeutic use*; D012405:Round Window, Ear / Q000187:drug effects*; D016559:Tacrolimus / Q000627:therapeutic use*
D000893:Anti-Inflammatory Agents; D007166:Immunosuppressive Agents; D003907:Dexamethasone; D016572:Cyclosporine; D006433:Hemocyanins; D011239:Prednisolone; C032808:keyhole-limpet hemocyanin; D005472:Fluorouracil; D016559:Tacrolimus