Evidence Supporting the Hypothesis That Inflammation-Induced Vasospasm Is Involved in the Pathogenesis of Acquired Sensorineural Hearing Loss

Abstract

Sensorineural hearing loss is mainly acquired and affects an estimated 1.3 billion humans worldwide. It is related to aging, noise, infection, ototoxic drugs, and genetic defects. It is essential to identify reversible and preventable causes to be able to reduce the burden of this disease. Inflammation is involved in most causes and leads to tissue injury through vasospasm-associated ischemia. Vasospasm is reversible. This review summarized evidence linking inflammation-induced vasospasm to several forms of acquired sensorineural hearing loss. The link between vasospasm and sensorineural hearing loss is directly evident in subarachnoid haemorrhage, which involves the release of vasoconstriction-inducing cytokines like interleukin-1, endothelin-1, and tumour necrosis factor. These proinflammatory cytokines can also be released in response to infection, autoimmune disease, and acute or chronically increased inflammation in the ageing organism as in presbyacusis or in noise-induced cochlear injury. Evidence of vasospasm and hearing loss has also been discovered in bacterial meningitis and brain injury. Resolution of inflammation-induced vasospasm has been associated with improvement of hearing in autoimmune diseases involving overproduction of interleukin-1 from inflammasomes. There is mainly indirect evidence for vasospasm-associated sensorineural hearing loss in most forms of systemic or injury- or infection-induced local vascular inflammation. This opens up avenues in prevention and treatment of vascular and systemic inflammation as well as vasospasm itself as a way to prevent and treat most forms of acquired sensorineural hearing loss. Future research needs to investigate interventions antagonising vasospasm and vasospasm-inducing proinflammatory cytokines and their production in randomised controlled trials of prevention and treatment of acquired sensorineural hearing loss. Prime candidates for interventions are hereby inflammasome inhibitors and vasospasm-reducing drugs like nitric oxide donors, rho-kinase inhibitors, and magnesium which have the potential to reduce sensorineural hearing loss in meningitis, exposure to noise, brain injury, arteriosclerosis, and advanced age-related and autoimmune disease-related inflammation.

Figure 1

Flow chart of literature search.

Figure 2

Mechanism of action of interleukin-1 (IL-1) via G-protein coupled receptors (GPCR) on reduction of nitric oxide (NO) production by reducing nitric oxide synthase (NOS) activity in the vascular endothelial cell (EC) and by activation of the enzyme Rho kinase via RhoA in the vascular smooth muscle cell to activate by phosphorylation through protein kinase C (PKC) myosine phosphatase targeting subunit-1 (MYPT1), protein kinase C-potentiated phosphatase inhibitor-17 (CPI-17 and myosine binding subunit (MBS)), which all three inhibit the myosine light chain phosphatase (MLCP) which dephosphorylates the myosine light chain, a process, which is necessary for smooth muscle relaxation. This process thus causes vasoconstriction.