Diagnostic and Prognostic Utility of Measuring Tumor Necrosis Factor in the Peripheral Circulation of Patients With Immune-Mediated Sensorineural Hearing Loss

Svrakic, Maja; Pathak, Shresh; Goldofsky, Eliot; Hoffman, Ronald A.; Chandrasekhar, Sujana S.; Sperling, Neil M.; Alexiades, George; Ashbach, Matthew; Vambutas, Andrea

doi:10.1001/2013.jamaoto.76

Cited by 35 publications

(46 citation statements)

References 17 publications

(30 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Recently, we have identified a role of TNF-α in steroid-sensitive and IL-1β in steroid-resistant immune mediated hearing loss [2, 3]. Furthermore, in a small cohort of patients, local administration of the TNF-α inhibitor etanercept by intratympanic injection was able to maintain hearing when systemic corticosteroid therapy was tapered [4], although use of systemic etanercept met with less promising efficacy [5, 6].…”

Section: Introductionmentioning

confidence: 99%

“…NAC therapy also reduced disease severity in a clinical trial of systemic lupus erythematosus (SLE), although the mechanism was ascribed to blocking the mammalian target of rapamycin in T cells [29]. Based on our prior observations that steroid sensitive AIED patients exhibit higher pre-treatment levels of TNF-α [2], we hypothesized that this elevated TNF-α induces expression of MPO which results in oxidative damage and further hearing loss. We further hypothesized that treatment with NAC can partially abrogate TNF-α mediated induction of MPO and subsequent oxidative damage making it a good candidate to be used for adjunct therapy.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

N-Acetylcysteine attenuates tumor necrosis factor alpha levels in autoimmune inner ear disease patients

2015

Self Cite

View full text Add to dashboard Cite

Autoimmune Inner Ear Disease (AIED) is a poorly understood disease marked by bilateral, rapidly progressive hearing loss triggered by unknown stimuli, which is corticosteroid responsive in 60% of patients. Although the mechanism of the disease is not precisely understood, a complex interaction of cytokines is believed to contribute towards the inflammatory disease process and hearing loss. Previously we showed the role of TNF-α in steroid-sensitive, and IL-1β in steroid-resistant immune mediated hearing loss. N-acetylcysteine (NAC), a broad spectrum antioxidant, has been effective in other autoimmune disorders. Other studies have shown NAC to have a protective adjunct role in human idiopathic sudden hearing loss, where the addition of NAC resulted in better hearing recovery than with steroids alone, although the mechanism of this protection was not elucidated. In the present study, we observed PBMCs from AIED patients exhibited higher baseline TNF-α and MPO levels compared to normal healthy controls. NAC effectively abrogates LPS-mediated TNF-α release from PBMC of both AIED patients and controls. We demonstrated that in AIED patients, the TNF-α down-stream signaling pathway appears aberrantly regulated, influencing both MPO and IL-8 expression. Given that NAC effectively abrogated LPS mediated TNF-α release and exerted minimal effects on the downstream targets of this pathway, we feel NAC may be a rational adjunct therapy for this enigmatic disease, worthy of clinical exploration.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

N-Acetylcysteine attenuates tumor necrosis factor alpha levels in autoimmune inner ear disease patients

2015

Self Cite

View full text Add to dashboard Cite

show abstract

“…Since increasing evidence shows that atherosclerosis is a chronic vascular inflammatory disorder and inflammatory reaction plays a significant role in the onset and development of cardiovascular disease [Liu et al, 2016;Tuttolomondo et al, 2012], researchers began to consider the chronic inflammation as a cause of SSNHL. Sahin et al [Svrakic et al, 2012] found a high level of neutrophils, tumor necrosis factor (TNF) and C-reactive protein in the patients with SSNHL. Berrettini et al [2013] provided imaging evidence for the involvement of inflammation in the inner ear among SSNHL patients through three-dimensional fluid-attenuated inversion recovery magnetic resonance imaging (3D-FLAIR MRI).…”

Section: Association Between Inflammation-related Genes and Ssnhlmentioning

confidence: 99%

Genetic Polymorphisms and Susceptibility to Sudden Sensorineural Hearing Loss: A Systematic Review

et al. 2019

View full text Add to dashboard Cite

Background: Recently, genetic factors have been considered as an important risk factor for sudden sensorineural hearing loss (SSNHL). Many studies analyzed the association between SSNHL and polymorphisms. However, most of them gave inconclusive results. Key Message: We performed a systematic review to find out the association between polymorphisms and susceptibility to SSNHL. Finally, 47 studies involving 5,230 SSNHL patients and 68 genes were included for analysis and discussion of results. Polymorphisms in 26 genes have been suggested to be correlated with the susceptibility to SSNHL. Summary: Although a great number of studies support that polymorphisms in genes are associated with susceptibility to SSNHL, we need large multicenter studies, which evaluate multiple single nucleotide polymorphisms in SSNHL patients, to find real genetic risk factors for susceptibility to SSNHL. This is very helpful in designing more effective prevention and treatment strategies for patients with SSNHL.

show abstract

“…However, studies over the last decade have shown that inflammatory and immune response in the cochlea play a role in noise‐induced hearing loss and that a variety of inflammatory cytokines are expressed in the cochlea in response to noxious stimuli such as acoustic trauma (Fujioka et al ., 2014). Among the pro‐inflammatory cytokines, tumor necrosis factor‐alpha (TNF‐α) has been shown to play a role in the loss of cochlear sensory hair cells in animal models (Demirhan et al ., 2013) and to contribute to sensorineural hearing loss in humans (Svrakic et al ., 2012). Specifically, exogenous TNF‐α induced loss of hair cells in rat Organ of Corti explants and this TNF‐α‐induced ototoxicity involved the upregulation of a series of apoptosis‐related genes (Dinh et al ., 2008).…”

Section: Introductionmentioning

confidence: 99%

“…Elevated levels of TNF‐α have been detected in inner ears after exposure to noise (Fujioka et al ., 2006) and ototoxic medications (Park et al ., 2012). In humans, elevated TNF‐α serum levels have been detected in people with idiopathic sudden sensorineural hearing loss (Demirhan et al ., 2013) and immune‐medicated sensorineural hearing loss (Svrakic et al ., 2012). …”

Section: Introductionmentioning

confidence: 99%

Activation of TRAIL‐DR5 pathway promotes sensorineural degeneration in the inner ear

et al. 2016

View full text Add to dashboard Cite

SummaryTumor necrosis factor (TNF) family cytokines are important mediators of inflammation. Elevated levels of serum TNF‐α are associated with human sensorineural hearing loss via poorly understood mechanisms. We demonstrate, for the first time, expression of TNF‐related apoptosis‐inducing ligand (TRAIL) and its signaling death receptor 5 (DR5) in the murine inner ear and show that exogenous TRAIL can trigger hair cell and neuronal degeneration, which can be partly prevented with DR5‐blocking antibodies.

show abstract

Diagnostic and Prognostic Utility of Measuring Tumor Necrosis Factor in the Peripheral Circulation of Patients With Immune-Mediated Sensorineural Hearing Loss

Cited by 35 publications

References 17 publications

N-Acetylcysteine attenuates tumor necrosis factor alpha levels in autoimmune inner ear disease patients

N-Acetylcysteine attenuates tumor necrosis factor alpha levels in autoimmune inner ear disease patients

Genetic Polymorphisms and Susceptibility to Sudden Sensorineural Hearing Loss: A Systematic Review

Activation of TRAIL‐DR5 pathway promotes sensorineural degeneration in the inner ear

Contact Info

Product

Resources

About