Intratympanic immunosuppressives for prevention of immune-mediated sensorineural hearing loss.

The American journal of otology Pub Date : 2000-07-01

G S Yang, H T Song, E M Keithley, J P Harris

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Abstract

Hypothesis: 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.

Conclusion: Local application of immunosuppressives did not suppress inner ear inflammatory infiltrates and hearing loss in KLH-induced labyrinthitis in a guinea pig model.

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鼓室内免疫抑制剂预防免疫介导的感音神经性听力损失。

假设:在无菌迷路炎豚鼠模型中，圆形窗膜应用免疫抑制剂可减少耳蜗炎症和听力损失。背景:全身性免疫抑制剂用于治疗由炎症(自身免疫、细菌、病毒)引起的感音神经性听力损失，在动物模型中，炎症会导致听力损失。跨腹膜应用药物是一种有吸引力且可能有效的治疗方法，可避免全身毒性。方法:采用锁孔帽贝血青素(KLH)制备无菌迷路炎。地塞米松(0.048 mg/d和0.288 mg/d)、环孢子素(0.5%)、醋酸泼尼松龙(1%)、氟尿嘧啶(5%)和FK506(0.01%)分别通过一次注射(填充中耳间隙)或渗透微型泵注入圆窗膜。通过听性脑干反应和组织学评价疗效。结果:没有药物能有效降低听力损失或炎症。结论:局部应用免疫抑制剂对豚鼠klh迷路炎模型内耳炎症浸润及听力损失无明显抑制作用。

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The American journal of otology

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