Cause of idiopathic sudden sensorineural hearing loss:The stress response theory

The stress response theory is a relatively new concept about the cause of idiopathic sudden sensorineural hearing loss(ISHL). A number of possible etiologies have been proposed in the literature, as discussed in this paper, but each proposed etiology has been both supported and refuted in the literature. However, the stress response theory can integrate hypotheses that have been advocated so far. The word "stress" refers to a constellation of physical and psychological stimuli including systemic viral and bacterial illness, systemic inflammatory disorders, and physical, mental or metabolic stress. Numerous studies have demonstrated adverse effects of systemic stress on health. Stress causes changes in the immune system and cytokine network through activation of the hypothalamus-pituitary-adrenal axis and the sympathetic nervous system. Several types of catecholamine and cytokine receptors are in the cochlea cells other than capillary cells, and then they can respond to systemic stressors. However, there are few studies examining how systemic stress is associated with cochlear dysfunction. The stress response theory addresses this question. In the theory, a variety of stressors and risk factors contribute to the onset of ISHL in varying degrees. The lateral wall of the cochlea has very unique responses to systemic stressors. It plays a critical role in causing ISHL. Systemic stressors converge at the lateral wall and trigger pathological activation of nuclear factor κ-light-chain-enhancer of activated B cells, a transcriptional factor known as a stress sensor. This activation enhances local expression of genes associated with immune and inflammatory system, resulting in cochlear dysfunction. We review the original stress response theory advocated by Adams et al and the integrative stress response theory that integrates our knowledge about the etiologies of ISHL so far.