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The Role of Tumor Necrosis Factor Alpha (TNFα) in Hearing Loss and Vestibular Schwannomas

  • Otology (A Vambutas, Section Editor)
  • Published:
Current Otorhinolaryngology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

The aim of this review is to highlight relevant literature on the role of tumor necrosis factor alpha (TNFα) in sensorineural hearing loss (SNHL) and vestibular schwannomas (VS).

Recent Findings

A comprehensive review of publically available databases including PubMed was performed. The mechanism by which hearing loss occurs in VS is still unknown and likely multifactorial. Genetic differences between VSs and tumor-secreted proteins may be responsible, at least in part, for VS-associated SNHL. TNFα has pleotropic roles in promoting inflammation, maintaining cellular homeostasis, inducing apoptosis, and mediating ototoxicity in patients with sporadic VS. TNFα-targeted therapies have shown efficacy in both animal models of sensorineural hearing loss and clinical trials in patients with immune-mediated hearing loss. Efforts are underway to develop nanotechnology-based methods to target TNFα and other pathogenic molecules in VS.

Summary

Development of molecularly targeted therapies against TNFα represents an important area of research in ameliorating VS-associated hearing loss.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Mahaley MS, Mettlin C, Natarajan N, Laws ER, Peace BB. Analysis of patterns of care of brain tumor patients in the United States: a study of the brain tumor section of the AANS and the CNS and the Commission on Cancer of the ACS. Clin Neurosurg. 1990;36:347–52.

    PubMed  Google Scholar 

  2. Thakur JD, Banerjee AD, Khan IS, Sonig A, Shorter CD, Gardner GL, et al. An update on unilateral sporadic small vestibular schwannoma. Neurosurg Focus. 2012;33(3):E1. https://doi.org/10.3171/2012.6.FOCUS12144.

    Article  PubMed  Google Scholar 

  3. Jacob A, Oblinger J, Bush ML, et al. Preclinical validation of AR42, a novel histone deacetylase inhibitor, as treatment for vestibular schwannomas. Laryngoscope. 2012;122:174–89.

    Article  CAS  PubMed  Google Scholar 

  4. Goutagny S, Raymond E, Esposito-Farese M, Trunet S, Mawrin C, Bernardeschi D, et al. Phase II study of mTORC1 inhibition by everolimus in neurofibromatosis type 2 patients with growing vestibular schwannomas. J Neuro-Oncol. 2015;122(2):313–20. https://doi.org/10.1007/s11060-014-1710-0.

    Article  CAS  Google Scholar 

  5. Sugarman BJ, Aggarwal BB, Hass PE, Figari IS, Palladino MA, Shepard HM. Recombinant human tumor necrosis factor-alpha: effects on proliferation of normal and transformed cells in vitro. Science. 1985;230(4728):943–5. https://doi.org/10.1126/science.3933111.

    Article  CAS  PubMed  Google Scholar 

  6. Braumüller H, Wieder T, Brenner E, et al. T-helper-1-cell cytokines drive cancer into senescence. Nature. 2013;494:361–5.

    Article  PubMed  Google Scholar 

  7. Zhao X, Rong L, Zhao X, Rong L, Zhao X, Li X, et al. TNF signaling drives myeloid-derived suppressor cell accumulation. J Clin Invest. 2012;122(11):4094–104. https://doi.org/10.1172/JCI64115.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Elinav E, Nowarski R, Thaiss CA, Hu B, Jin C, Flavell RA. Inflammation-induced cancer: crosstalk between tumours, immune cells and microorganisms. Nat Rev Cancer. 2013;13(11):759–71. https://doi.org/10.1038/nrc3611.

    Article  CAS  PubMed  Google Scholar 

  9. Roosli C, Linthicum FH, Cureoglu S, Merchant SN. Dysfunction of the cochlea contributing to hearing loss in acoustic neuromas: an underappreciated entity. Otol Neurotol. 2012;33(3):473–80. https://doi.org/10.1097/MAO.0b013e318248ee02.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Matthies C, Samii M. Management of 1000 vestibular schwannomas (acoustic neuromas): clinical presentation. Neurosurgery. 1997;40(1):10.

    Google Scholar 

  11. (1996) The early history of the neurofibromatoses: evolution of the concept of neurofibromatosis type 2. Arch Otolaryngol Head Neck Surg 122:1240–1249.

  12. Nadol JB, Diamond PF, Thornton AR. Correlation of hearing loss and radiologic dimensions of vestibular schwannomas (acoustic neuromas). Am J Otol. 1996;17(2):312–6.

    PubMed  Google Scholar 

  13. Caye-Thomasen P, Dethloff T, Hansen S, Stangerup S-E, Thomsen J. Hearing in patients with intracanalicular vestibular schwannomas. Audiol Neurotol. 2007;12, 12(1)

  14. Gouveris HT, Victor A, Mann WJ. Cochlear origin of early hearing loss in vestibular schwannoma. Laryngoscope. 2007;117:680–3.

    Article  PubMed  Google Scholar 

  15. Stankovic KM, Mrugala MM, Martuza RL, Silver M, Betensky RA, Nadol JB, et al. Genetic determinants of hearing loss associated with vestibular schwannomas. Otol Neurotol. 2009;30(5):661–7. https://doi.org/10.1097/MAO.0b013e3181a66ece.

    Article  PubMed  Google Scholar 

  16. Lassaletta L, Martínez-Glez V, Torres-Martín M, Rey JA, Gavilán J. cDNA microarray expression profile in vestibular schwannoma: correlation with clinical and radiological features. Cancer Genet Cytogenet. 2009;194(2):125–7. https://doi.org/10.1016/j.cancergencyto.2009.06.016.

    Article  CAS  PubMed  Google Scholar 

  17. Silverstein H. A rapid protein test for acoustic neurinoma. Arch Otolaryngol. 1972;95(3):202–4. https://doi.org/10.1001/archotol.1972.00770080344003.

    Article  CAS  PubMed  Google Scholar 

  18. Silverstein H. Labyrinthine tap as a diagnostic test for acoustic neurinoma. Otolaryngol Clin N Am. 1973;6(1):229–44.

    CAS  Google Scholar 

  19. Schmitt HA, Pich A, Schröder A, Scheper V, Lilli G, Reuter G, et al. Proteome analysis of human perilymph using an intraoperative sampling method. J Proteome Res. 2017;16(5):1911–23. https://doi.org/10.1021/acs.jproteome.6b00986.

    Article  CAS  PubMed  Google Scholar 

  20. Lysaght AC, Kao S-Y, Paulo JA, Merchant SN, Steen H, Stankovic KM. Proteome of human perilymph. J Proteome Res. 2011;10(9):3845–51. https://doi.org/10.1021/pr200346q.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Ji H, Cao R, Yang Y, et al. TNFR1 mediates TNF-α-induced tumour lymphangiogenesis and metastasis by modulating VEGF-C-VEGFR3 signalling. Nat Commun. 2014;5:4944.

    Article  CAS  PubMed  Google Scholar 

  22. Brieger J, Bedavanija A, Lehr H-A, Maurer J, Mann WJ. Expression of angiogenic growth factors in acoustic neurinoma. Acta Otolaryngol. 2016;123:1040–5.

    Article  Google Scholar 

  23. • Plotkin SR, Stemmer-Rachamimov AO, Barker FG, Halpin C, Padera TP, Tyrrell A, et al. Hearing improvement after bevacizumab in patients with neurofibromatosis type 2. N Engl J Med. 2009;361:358–67. First demonstration that VEGF blockade can improve hearing in patients with NF2 vestibular schwannomas.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Plotkin SR, Merker VL, Halpin C, Jennings D, McKenna MJ, Harris GJ, et al. Bevacizumab for progressive vestibular schwannoma in neurofibromatosis type 2: a retrospective review of 31 patients. Otol Neurotol. 2012;33(6):1046–52. https://doi.org/10.1097/MAO.0b013e31825e73f5.

    Article  PubMed  Google Scholar 

  25. Carswell EA, Old LJ, Kassel RL, Green S, Fiore N, Williamson B. An endotoxin-induced serum factor that causes necrosis of tumors. Proc Natl Acad Sci U S A. 1975;72(9):3666–70. https://doi.org/10.1073/pnas.72.9.3666.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Pennica D, Nedwin GE, Hayflick JS, Seeburg PH, Derynck R, Palladino MA, et al. Human tumour necrosis factor: precursor structure, expression and homology to lymphotoxin. Nature. 1984;312(5996):724–9. https://doi.org/10.1038/312724a0.

    Article  CAS  PubMed  Google Scholar 

  27. Gray PW, Aggarwal BB, Benton CV, Bringman TS, Henzel WJ, Jarrett JA, et al. Cloning and expression of cDNA for human lymphotoxin, a lymphokine with tumour necrosis activity. Nature. 1984;312(5996):721–4. https://doi.org/10.1038/312721a0.

    Article  CAS  PubMed  Google Scholar 

  28. Aggarwal BB, Kohr WJ, Hass PE, Moffat B, Spencer SA, Henzel WJ, et al. Human tumor necrosis factor. Production, purification, and characterization. J Biol Chem. 1985;260(4):2345–54.

    CAS  PubMed  Google Scholar 

  29. Probert L. TNF and its receptors in the CNS: the essential, the desirable and the deleterious effects. Neuroscience. 2015;302:2–22. https://doi.org/10.1016/j.neuroscience.2015.06.038.

    Article  CAS  PubMed  Google Scholar 

  30. Papathanasiou S, Rickelt S, Soriano ME, Schips TG, Maier HJ, Davos CH, et al. Tumor necrosis factor-α confers cardioprotection through ectopic expression of keratins K8 and K18. Nat Med. 2015;21(9):1076–84. https://doi.org/10.1038/nm.3925.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Zhao S, Yin KW, Goodson NJ. FRI0134 association between vitamin D deficiency and markers of disease activity in axial spondyloarthritis: table 1. Ann Rheum Dis. 2014;73(Suppl 2):430.2–430. https://doi.org/10.1136/annrheumdis-2014-eular.2134.

    Article  Google Scholar 

  32. Zou J, Pyykko I, Sutinen P, Toppila E. Vibration induced hearing loss in guinea pig cochlea: expression of TNF-alpha and VEGF. Hear Res. 2005;202(1-2):13–20. https://doi.org/10.1016/j.heares.2004.10.008.

    Article  CAS  PubMed  Google Scholar 

  33. Riva C, Donadieu E, Magnan J, Lavieille J-P. Age-related hearing loss in CD/1 mice is associated to ROS formation and HIF target proteins up-regulation in the cochlea. Exp Gerontol. 2007;42(4):327–36. https://doi.org/10.1016/j.exger.2006.10.014.

    Article  CAS  PubMed  Google Scholar 

  34. Satoh H, Firestein GS, Billings PB, Harris JP, Keithley EM. Tumor necrosis factor-alpha, an initiator, and etanercept, an inhibitor of cochlear inflammation. Laryngoscope. 2002;112(9):1627–34. https://doi.org/10.1097/00005537-200209000-00019.

    Article  CAS  PubMed  Google Scholar 

  35. Fujioka M, Kanzaki S, Okano HJ, Masuda M, Ogawa K, Okano H. Proinflammatory cytokines expression in noise-induced damaged cochlea. J Neurosci Res. 2006;83(4):575–83. https://doi.org/10.1002/jnr.20764.

    Article  CAS  PubMed  Google Scholar 

  36. MacArthur CJ, Pillers DA, Pang J, Kempton JB, Trune DR. Altered expression of middle and inner ear cytokines in mouse otitis media. Laryngoscope. 2011;121(2):365–71. https://doi.org/10.1002/lary.21349.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Trune DR, Larrain BE, Hausman FA, Kempton JB, MacArthur CJ. Simultaneous measurement of multiple ear proteins with multiplex ELISA assays. Hear Res. 2011;275(1-2):1–7. https://doi.org/10.1016/j.heares.2010.11.009.

    Article  CAS  PubMed  Google Scholar 

  38. Perny M, Roccio M, Grandgirard D, Solyga M, Senn P, Leib SL. The severity of infection determines the localization of damage and extent of sensorineural hearing loss in experimental pneumococcal meningitis. J Neurosci. 2016;36(29):7740–9. https://doi.org/10.1523/JNEUROSCI.0554-16.2016.

    Article  CAS  PubMed  Google Scholar 

  39. So H, Kim H, Lee JH, et al. Cisplatin cytotoxicity of auditory cells requires secretions of proinflammatory cytokines via activation of ERK and NF-kappaB. J Assoc Res Otolaryngol. 2007;8(3):338–55. https://doi.org/10.1007/s10162-007-0084-9.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Kim HJ, Oh GS, Lee JH, Lyu AR, Ji HM, Lee SH, et al. Cisplatin ototoxicity involves cytokines and STAT6 signaling network. Cell Res. 2011;21(6):944–56. https://doi.org/10.1038/cr.2011.27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Kaur T, Mukherjea D, Sheehan K, Jajoo S, Rybak LP, Ramkumar V. Short interfering RNA against STAT1 attenuates cisplatin-induced ototoxicity in the rat by suppressing inflammation. Cell Death Dis. 2011;2(7):e180. https://doi.org/10.1038/cddis.2011.63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Hoang KN, Dinh CT, Bas E, Chen S, Eshraghi AA, Van De Water TR. Dexamethasone treatment of naive organ of Corti explants alters the expression pattern of apoptosis-related genes. Brain Res. 2009;1301:1–8.

    Article  CAS  PubMed  Google Scholar 

  43. Bas E, Van De Water TR, Gupta C, Dinh J, Vu L, Martinez-Soriano F, et al. Efficacy of three drugs for protecting against gentamicin-induced hair cell and hearing losses. Br J Pharmacol. 2012;166(6):1888–904. https://doi.org/10.1111/j.1476-5381.2012.01890.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Pasparakis M. Immune and inflammatory responses in TNF alpha-deficient mice: a critical requirement for TNF alpha in the formation of primary B cell follicles, follicular dendritic cell networks and germinal centers, and in the maturation of the humoral immune response. J Exp Med. 1996;184(4):1397–411. https://doi.org/10.1084/jem.184.4.1397.

    Article  CAS  PubMed  Google Scholar 

  45. Erickson SL, de Sauvage FJ, Kikly K, Carver-Moore K, Pitts-Meek S, Gillett N, et al. Decreased sensitivity to tumour-necrosis factor but normal T-cell development in TNF receptor-2-deficient mice. Nature. 1994;372(6506):560–3. https://doi.org/10.1038/372560a0.

    Article  CAS  PubMed  Google Scholar 

  46. Pfeffer K, Matsuyama T, Kündig TM, Wakeham A, Kishihara K, Shahinian A, et al. Mice deficient for the 55 kd tumor necrosis factor receptor are resistant to endotoxic shock, yet succumb to L. monocytogenes infection. Cell. 1993;73(3):457–67. https://doi.org/10.1016/0092-8674(93)90134-C.

    Article  CAS  PubMed  Google Scholar 

  47. Rothe J, Lesslauer W, Lötscher H, Lang Y, Koebel P, Köntgen F, et al. Mice lacking the tumour necrosis factor receptor 1 are resistant to IMF-mediated toxicity but highly susceptible to infection by Listeria monocytogenes. Nature. 1993;364(6440):798–802. https://doi.org/10.1038/364798a0.

    Article  CAS  PubMed  Google Scholar 

  48. Yang S, Zhang LS, Gibboni R, Weiner B, Bao S. Impaired development and competitive refinement of the cortical frequency map in tumor necrosis factor-deficient mice. Cereb Cortex. 2014;24(7):1956–65. https://doi.org/10.1093/cercor/bht053.

    Article  PubMed  Google Scholar 

  49. Oishi N, Chen J, Zheng H-W, Hill K, Schacht J, Sha S-H. Tumor necrosis factor-alpha-mutant mice exhibit high frequency hearing loss. J Assoc Res Otolaryngol. 2013;14(6):801–11. https://doi.org/10.1007/s10162-013-0410-3.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Sharaf K, Ihler F, Bertlich M, Reichel CA, Berghaus A, Canis M. Tumor necrosis factor-induced decrease of Cochlear blood flow can be reversed by etanercept or JTE-013. Otol Neurotol. 2016;37:e203–8.

    Article  PubMed  Google Scholar 

  51. Ihler F, Sharaf K, Bertlich M, Strieth S, Reichel CA, Berghaus A, et al. Etanercept prevents decrease of cochlear blood flow dose-dependently caused by tumor necrosis factor alpha. Ann Otol Rhinol Laryngol. 2013;122(7):468–73. https://doi.org/10.1177/000348941312200711.

    Article  PubMed  Google Scholar 

  52. Arpornchayanon W, Canis M, Ihler F, Settevendemie C, Strieth S. TNF-alpha inhibition using etanercept prevents noise-induced hearing loss by improvement of cochlear blood flow in vivo. Int J Audiol. 2013;52:545–52.

    Article  PubMed  Google Scholar 

  53. Ihler F, Pelz S, Coors M, Matthias C, Canis M. Application of a TNF-alpha-inhibitor into the scala tympany after cochlear electrode insertion trauma in guinea pigs: preliminary audiologic results. Int J Audiol. 2014;53:810–6.

    Article  PubMed  Google Scholar 

  54. Lobo D, García-Berrocal JR, Trinidad A, Verdaguer JM, Ramírez-Camacho R. Review of the biological agents used for immune-mediated inner ear disease. Acta Otorrinolaringologica (English Edition). 2013;64(3):223–9. https://doi.org/10.1016/j.otoeng.2013.06.005.

    Article  Google Scholar 

  55. Matteson EL, Tirzaman O, Kasperbauer J, Facer GW, Beatty CW, Fabry DA, et al. Use of methotrexate for autoimmune hearing loss. Ann Otol Rhinol Laryngol. 2016;109:710–4.

    Article  Google Scholar 

  56. McCabe BF. Autoimmune sensorineural hearing loss. Ann Otol Rhinol Laryngol. 1979;88(5):585–9. https://doi.org/10.1177/000348947908800501.

    Article  CAS  PubMed  Google Scholar 

  57. Demirhan E, Eskut NP, Zorlu Y, Cukurova I, Tuna G, Kirkali FG. Blood levels of TNF-α, IL-10, and IL-12 in idiopathic sudden sensorineural hearing loss. Laryngoscope. 2013;123(7):1778–81. https://doi.org/10.1002/lary.23907.

    Article  CAS  PubMed  Google Scholar 

  58. Scherer EQ, Yang J, Canis M, et al. Tumor necrosis factor-α enhances microvascular tone and reduces blood flow in the cochlea via enhanced sphingosine-1-phosphate signaling. Stroke. 2010;41:2618–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Haubner F, Martin L, Steffens T, Strutz J, Kleinjung T. The role of soluble adhesion molecules and cytokines in sudden sensorineural hearing loss. YMHN. 2011;144:575–80.

    Google Scholar 

  60. Derebery MJ, Rao VS, Siglock TJ, Linthicum FH, Nelson RA. Menière’s disease: an immune complex-mediated illness? Laryngoscope. 1991;101(3):225–9. https://doi.org/10.1288/00005537-199103000-00001.

    Article  CAS  PubMed  Google Scholar 

  61. Nacci A, Dallan I, Monzani F, Dardano A, Migliorini P, Riente L, et al. Elevated antithyroid peroxidase and antinuclear autoantibody titers in Ménière’s disease patients: more than a chance association? Audiol Neurootol. 2010;15(1):1–6. https://doi.org/10.1159/000218357.

    Article  CAS  PubMed  Google Scholar 

  62. Gazquez I, Soto-Varela A, Aran I, Santos S, Batuecas A, Trinidad G, et al. High prevalence of systemic autoimmune diseases in patients with Meniere’s disease. PLoS One. 2011;6(10):e26759. https://doi.org/10.1371/journal.pone.0026759.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. • Dilwali S, Landegger LD, Soares VY, Deschler DG, Stankovic KM. Secreted factors from human vestibular schwannomas can cause Cochlear damage. Sci Rep. 2015;5:18599. First demonstration that VS secretions rich in TNFα can cause direct cochlear damage.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. van Wijk F, Staecker H, Keithley E, Lefebvre PP. Local perfusion of the tumor necrosis factor α blocker infliximab to the inner ear improves autoimmune neurosensory hearing loss. Audiol Neurotol. 2006;11(6):357–65. https://doi.org/10.1159/000095897.

    Article  Google Scholar 

  65. Derebery MJ, Fisher LM, Voelker CCJ, Calzada A. An open label study to evaluate the safety and efficacy of intratympanic golimumab therapy in patients with autoimmune inner ear disease. Otol Neurotol. 2014;35(9):1515–21. https://doi.org/10.1097/MAO.0000000000000566.

    Article  PubMed  Google Scholar 

  66. Gazeau P, Saraux A, Devauchelle-Pensec V, Cornec D. Long-term efficacy of infliximab in autoimmune sensorineural hearing loss associated with rheumatoid arthritis. Rheumatology. 2014;53(9):1715–6. https://doi.org/10.1093/rheumatology/keu025.

    Article  CAS  PubMed  Google Scholar 

  67. Rahman MU, Poe DS, Choi HK. Etanercept therapy for immune-mediated cochleovestibular disorders: preliminary results in a pilot study. Otol Neurotol. 2001;22(5):619–24. https://doi.org/10.1097/00129492-200109000-00010.

    Article  CAS  PubMed  Google Scholar 

  68. Matteson EL, Choi HK, Poe DS, Wise C, Lowe VJ, Mcdonald TJ, et al. Etanercept therapy for immune-mediated cochleovestibular disorders: a multi-center, open-label, pilot study. Arthritis Rheum. 2005;53(3):337–42. https://doi.org/10.1002/art.21179.

    Article  CAS  PubMed  Google Scholar 

  69. • Cohen S, Shoup A, Weisman MH, Harris J. Etanercept treatment for autoimmune inner ear disease: results of a pilot placebo-controlled study. Otol Neurotol. 2005;26(5):903–7 Randomized controlled trial of etanercept treatment in patients with AIED. https://doi.org/10.1097/01.mao.0000185082.28598.87.

    Article  PubMed  Google Scholar 

  70. Taurone S, Bianchi E, Attanasio G, et al. Immunohistochemical profile of cytokines and growth factors expressed in vestibular schwannoma and in normal vestibular nerve tissue. Mol Med Rep. 2015;12:737–45.

    Article  CAS  PubMed  Google Scholar 

  71. • Ren Y, Sagers JE, Landegger LD, Bhatia SN, Stankovic KM. Tumor-penetrating delivery of siRNA against TNFα to human vestibular schwannomas. Sci Rep. 2017;7:12922. First demonstration that tumor-targeted nanotechnology and RNA interference can be leveraged synergistically to mitigate the secretion of ototoxic molecules including TNFα.

    Article  PubMed  PubMed Central  Google Scholar 

  72. Agnihotri S, Jalali S, Wilson MR, et al. The genomic landscape of schwannoma. Nat Genet. 2016;48:1339–48.

    Article  CAS  PubMed  Google Scholar 

  73. Jobin C, Morteau O, Han DS, Balfour Sartor R. Specific NF-kappaB blockade selectively inhibits tumour necrosis factor-alpha-induced COX-2 but not constitutive COX-1 gene expression in HT-29 cells. Immunology. 1998;95(4):537–43. https://doi.org/10.1046/j.1365-2567.1998.00646.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Feng L, Xia Y, Garcia GE, Hwang D, Wilson CB. Involvement of reactive oxygen intermediates in cyclooxygenase-2 expression induced by interleukin-1, tumor necrosis factor-alpha, and lipopolysaccharide. J Clin Investig. 1995;95:1669–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Dilwali S, Briët MC, Kao S-Y, Fujita T, Landegger LD, Platt MP, et al. Preclinical validation of anti-nuclear factor-kappa B therapy to inhibit human vestibular schwannoma growth. Mol Oncol. 2015;9(7):1359–70. https://doi.org/10.1016/j.molonc.2015.03.009.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Dilwali S, Kao S-Y, Fujita T, Landegger LD, Stankovic KM. Nonsteroidal anti-inflammatory medications are cytostatic against human vestibular schwannomas. Transl Res. 2015;166(1):1–11. https://doi.org/10.1016/j.trsl.2014.12.007.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Kandathil CK, Dilwali S, Wu C-C, Ibrahimov M, McKenna MJ, Lee H, et al. Aspirin intake correlates with halted growth of sporadic vestibular schwannoma in vivo. Otol Neurotol. 2014;35(2):353–7. https://doi.org/10.1097/MAO.0000000000000189.

    Article  PubMed  Google Scholar 

  78. Stankovic KM (2017) Study of aspirin in patients with vestibular schwannoma. In: https://clinicaltrials.gov/ct2/show/NCT03079999?term=stankovic&rank=1. ClinigalTrials.gov Identifier: NCT03079999. Accessed 30 Nov 2017.

  79. Hellgren K, Smedby KE, Feltelius N, Baecklund E, Askling J. Do rheumatoid arthritis and lymphoma share risk factors?: a comparison of lymphoma and cancer risks before and after diagnosis of rheumatoid arthritis. Arthritis Rheum. 2010;62(5):1252–8. https://doi.org/10.1002/art.27402.

    Article  PubMed  Google Scholar 

  80. Hellgren K, Smedby KE, Backlin C, Sundstrom C, Feltelius N, Eriksson JK, et al. Ankylosing spondylitis, psoriatic arthritis, and risk of malignant lymphoma: a cohort study based on nationwide prospectively recorded data from Sweden. Arthritis Rheumatol. 2014;66(5):1282–90. https://doi.org/10.1002/art.38339.

    Article  CAS  PubMed  Google Scholar 

  81. Baecklund E, Iliadou A, Askling J, et al. Association of chronic inflammation, not its treatment, with increased lymphoma risk in rheumatoid arthritis. Arthritis Rheum. 2006;54:692–701.

    Article  PubMed  Google Scholar 

  82. Burmester GR, Panaccione R, Gordon KB, McIlraith MJ, Lacerda APM. Adalimumab: long-term safety in 23 458 patients from global clinical trials in rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis and Crohn’s disease. Ann Rheum Dis. 2013;72(4):517–24. https://doi.org/10.1136/annrheumdis-2011-201244.

    Article  CAS  PubMed  Google Scholar 

  83. Wolfe F, Michaud K. The effect of methotrexate and anti-tumor necrosis factor therapy on the risk of lymphoma in rheumatoid arthritis in 19,562 patients during 89,710 person-years of observation. Arthritis Rheum. 2007;56(5):1433–9. https://doi.org/10.1002/art.22579.

    Article  CAS  PubMed  Google Scholar 

  84. Ramiro S, Sepriano A, Chatzidionysiou K, et al. Safety of synthetic and biological DMARDs: a systematic literature review informing the 2016 update of the EULAR recommendations for management of rheumatoid arthritis. Ann Rheum Dis. 2017;76:1101–36.

    Article  PubMed  Google Scholar 

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Funding

This work was supported by the CORE grant from American Academy of Otolaryngology—Head and Neck Surgery and the New England Otolaryngological Society research grant (Y.R.), NIH/NIDCD grant R01DC015824 (K.M.S.), the Bertarelli Foundation (K.M.S.), Nancy Sayles Day Foundation (K.M.S.), and the Lauer Tinnitus Research Center (K.M.S.).

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Authors and Affiliations

  1. Department of Otolaryngology, Massachusetts Eye and Ear, 243 Charles Street, Boston, MA, 02114, USA

    Yin Ren & Konstantina M. Stankovic

  2. Department of Otolaryngology, Harvard Medical School, 25 Shattuck St, Boston, MA, 02115, USA

    Yin Ren & Konstantina M. Stankovic

  3. Eaton Peabody Laboratories, Massachusetts Eye and Ear, 243 Charles Street, Boston, MA, 02114, USA

    Konstantina M. Stankovic

  4. Harvard Program in Speech and Hearing Bioscience and Technology, 25 Shattuck Street, Boston, MA, 02115, USA

    Konstantina M. Stankovic

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Correspondence to Konstantina M. Stankovic.

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Ren, Y., Stankovic, K.M. The Role of Tumor Necrosis Factor Alpha (TNFα) in Hearing Loss and Vestibular Schwannomas. Curr Otorhinolaryngol Rep 6, 15–23 (2018). https://doi.org/10.1007/s40136-018-0186-4

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