Immune-mediated Sensorineural Hearing Loss: Patho-Mechanisms and Therapeutic Strategies

Abstract

The immune system protects the inner ear from various infections. However, the fragile audiological and vestibular structures are damaged due to immune-related and inflammatory responses, thus resulting in sensorineural hearing loss. Immune-mediated sensorineural hearing loss (ISNHL) can either be of autoimmune or autoinflammatory origin, and studies have shown that ISNHL ultimately results from inflammatory responses in both the cases. Several disorders have been identified that either primarily cause hearing loss due to localized inflammation (such as Meniere's disease) or as an additional manifestation resulting from systemic inflammation (as seen in Muckle-Well syndrome). Immune molecularand patho-mechanisms have been proposed to explain ISNHL, yet it has been an enigma. A crucial mechanism leading to immune activation and inflammation involves the increased levels of NLRP3 inflammasome-associated IL-1β and TNF-α, in resident macrophages of the inner ear. The presence of autoantibodies to inner ear antigens have been reported as a causative ISNHL and these antibodies also serve as diagnostic markers. Genetic-susceptibility to ISNHL in some individuals has been reported. ISNHL is reversible, where hearing and vestibular functions can be restored. Several studies have put forward therapeutic strategies to alleviate hearing impairment, by usage of immunosuppressive drugs, monoclonal antibodies, IL-1β and TNF-α antagonists, and NLRP3 inflammasome-inhibitors. Emerging approaches for treating autoimmune disease include altering gut microbiota, stem cell therapy and precision medicine. The present report reviews the various molecular-and patho-mechanisms associated with ISNHL. It further focuses on possible therapeutic targets and the relevance in application of emerging therapeutic strategies to alleviate hearing loss.