Monocytes, Macrophages, and Microglia and the Role of IL-1 in Autoimmune Inner Ear Disease (AIED)
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Purpose of Review
Autoimmune inner ear disease (AIED) is a rare disease of unknown etiology characterized by a sudden decline in hearing. Although AIED is initially responsive to corticosteroid therapy, this response is lost over time. We recently demonstrated in a small cohort of corticosteroid-resistant AIED patients that IL-1 was overexpressed in the plasma and that IL-1 antagonism led to hearing improvement and reduction in circulating IL-1. Autoinflammatory diseases, such as Muckle-Wells syndrome (MWS), are diseases of the innate immune system whose phenotype includes sensorineural hearing loss. Monocytes are the primary cells orchestrating the inflammatory response in this family of diseases, due to a gain-of-function mutation that causes excessive IL-1 release.
We have observed that monocytes from AIED patients release excessive IL-1 and behave similarly to monocytes from Muckle-Wells patients, despite the lack of pathogenic mutations and other characteristic phenotypic manifestations. Unlike MWS, we have observed substantially greater hearing improvement with IL-1 antagonism than hearing improvement reported in MWS.
The role of monocytes, macrophages, and microglia and the cytokines they secrete are of critical importance in both understanding disease mechanism and identification of novel therapeutic targets to treat chronic inflammatory diseases of the cochlea such as AIED.
KeywordsInterleukin-1b (IL-1β) Tumor necrosis factor (TNF)-α Monocytes Macrophages Microglia AIED
Compliance with Ethical Standards
Patients with AIED were recruited from the practice of Dr. Vambutas under an IRB-approved study at Northwell Health System.
Conflict of Interest
Dr. Vambutas reports consulting for Sobi Pharmaceuticals, the patent has been abandoned.
Dr. Pathak has nothing to disclose.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
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