title: Diagnostic and prognostic utility of measuring tumor necrosis factor in the peripheral circulation of patients with immune-mediated sensorineural hearing loss.
abstract: OBJECTIVE
  To characterize levels of tumor necrosis factor (TNF; formerly known as tumor necrosis factor α), a well-established proinflammatory cytokine, in patients with immune-mediated sensorineural hearing loss (IM-SNHL) and to determine the role of this cytokine in identifying steroid-responsive hearing loss.
  
  
  METHODS
  Prospective case-control study.
  
  
  METHODS
  Tertiary care academic medical center.
  
  
  METHODS
  A total of 11 control subjects and 85 patients with clinical and audiometric characteristics of IM-SNHL (autoimmune inner ear disease and sudden SNHL combined) treated with corticosteroids were enrolled in the study. Patients were categorized as steroid responders (n = 47) and steroid nonresponders (n = 38). Peripheral venous blood was used to determine the total amount of plasma TNF by enzyme-linked immunosorbent assay. Peripheral blood mononuclear cells (PBMCs) were isolated and treated with in vitro dexamethasone. Treated and untreated PBMCs were then analyzed for release of soluble TNF protein into conditioned supernatants as well as expression of TNF messenger RNA (mRNA).
  
  
  METHODS
  Mean plasma levels of TNF, unstimulated and dexamethasone-stimulated PBMC-secreted levels of TNF, and TNF mRNA levels in unstimulated and dexamethasone-stimulated PBMCs.
  
  
  RESULTS
  Steroid nonresponders had the highest mean baseline plasma levels of TNF compared with steroid responders and control subjects (27.6, 24.1, and 14.4 pg/mL, respectively) (P = .03). For patients with IM-SNHL with a high baseline plasma levels of TNF (>14.4 pg/mL), the mean TNF secreted by PBMCs was 59.1 pg/mL, which decreased to 7.2 pg/mL with in vitro dexamethasone stimulation in the responder group, while the mean TNF secreted by PBMCs was 11.2 pg/mL, which slightly increased to 11.7 pg/mL with in vitro dexamethasone stimulation in the nonresponder group (P = .04).
  
  
  CONCLUSIONS
  The level of TNF can be used as both a diagnostic and prognostic cytokine for IM-SNHL. For patients presenting with a sudden change in hearing threshold, a high baseline plasma TNF from the peripheral circulation is supportive of the diagnosis if it is greater than 18.8 pg/mL, with a positive predictive value higher than 97%. In addition, this study demonstrates that for patients with IM-SNHL and high plasma levels of TNF, their clinical response to oral glucocorticoids can be predicted by their in vitro PBMC response to dexamethasone. This algorithm may further guide optimal medical treatment and possibly avoid the deleterious adverse effects of administering glucocorticoids to those patients who would not benefit from their effect.
authors.forename: Maja
authors.initials: M
authors.lastname: Svrakic
authors.forename: Shresh
authors.initials: S
authors.lastname: Pathak
authors.forename: Eliot
authors.initials: E
authors.lastname: Goldofsky
authors.forename: Ronald
authors.initials: R
authors.lastname: Hoffman
authors.forename: Sujana S
authors.initials: SS
authors.lastname: Chandrasekhar
authors.forename: Neil
authors.initials: N
authors.lastname: Sperling
authors.forename: George
authors.initials: G
authors.lastname: Alexiades
authors.forename: Matthew
authors.initials: M
authors.lastname: Ashbach
authors.forename: Andrea
authors.initials: A
authors.lastname: Vambutas
mesh_terms: D000046:Academic Medical Centers; D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002478:Cells, Cultured / Q000187:drug effects; D003907:Dexamethasone / Q000627:therapeutic use; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D006319:Hearing Loss, Sensorineural / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood* / Q000378:metabolism; D055815:Young Adult
chemical_list: D015415:Biomarkers; D005938:Glucocorticoids; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone