Proinflammatory and Proadhesive Activation of Lymphocytes and Macrophages in Sudden Sensorineural Hearing Loss

Abstract

Even though sudden sensorineural hearing loss (SHL) is a quite frequent disease, the pathogenetic processes leading to it are widely unknown. There is increasing evidence that immunomodulatory cells, especially T lymphocytes, might be involved. Twelve patients with acute SHL and 12 healthy, age-matched individuals were included in this study. In addition to routine blood parameters, plasma levels of tumor necrosis factor alpha (TNF-α), soluble CD40 (sCD40) and sCD40 ligand (sCD40L) were determined by ELISA. Moreover, peripheral blood mononuclear cells were isolated by Ficoll density gradient. Afterwards, in subpopulations – identified by CD14 (monocytes), CD68 (macrophages), CD3 (T lymphocytes) or CD19 (B lymphocytes) immunoreactivity – proinflammatory (CD40, TNF-α or cyclooxygenase-2) and proadhesive (CD38) proteins were measured by 2-color fluorescence-activated cell sorter analyses. In comparison with healthy individuals, patients with acute SHL revealed elevated plasma levels of sCD40 and sCD40L and a significantly decreased percentage (36%) of lymphocytes, especially of T lymphocytes (28%). Additionally, in patients with acute SHL the percentage of proinflammatory CD40, TNF-α, cyclooxygenase-2 or CD38-positive T or B lymphocytes was significantly increased. Our data suggest an enhanced extravasation of proadhesive and proinflammatory lymphocytes from the peripheral circulation, which may contribute to SHL disease induction as well as progression and, thus, may be suggested as a novel therapeutical target.

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

“…10 While some investigators reported that, in an animal model, etanercept has a protective effect on hearing loss, 11 others found it less effective than prednisone, with a greater potential for adverse effects. 4,6,12 In 2 small human studies, levels of TNF in patients with sudden SNHL were found to be elevated in one study of 12 patients, 13 while the other study showed that both corticosteroid-responding and nonresponding patients (total of 30 for both groups together) had lower levels of TNF than controls and concluded that this cytokine does not offer useful information in either prognosis or diagnosis of the disease.…”

Blood levels ofTNF‐α,IL‐10, andIL‐12in idiopathic sudden sensorineural hearing loss

“…1 Although SSNHL is a wellrecognized condition, no standard definition or treatment protocol has been accepted. [3][4][5][6][7][8][9] But none of the theories alone can explain the etiopathogenesis of ISSNHL, which most probably is multifactorial in etiology. 2 A number of theories have been hypothesized to explain the etiopa-thogenesis of ISSNHL, including infectious diseases, vascular occlusion, ruptures in the cochlear membrane, immune mediated mechanisms, and abnormal cellular stress responses within the cochlea.…”

“…7,10 It is now clear that the inner ear is not an ''immunologically privileged'' site, and according to recent studies 11,12 there is increasing evidence of immune mediated mechanisms in the etiopathogenesis of ISSNHL. However, some studies have shown the existence of a local immune response within the inner ear, with an enhanced transmigration of immunocompetent cells from the bloodstream.…”

The Expression of AGO2 and DGCR8 in Idiopathic Sudden Sensorineural Hearing Loss

“…It has been reported that WBC counts are a biomarker related to systemic stress and cochlear inflammation [25]. Additionally, several systemic inflammatory processes can be detected by examination of the blood, which may also be a very promising approach for monitoring possible pathogenetic mechanisms associated with SSNHL [26]. In this study, downregulated AGO2 mRNA expression level (I, 11.89±1.15; III, 9.54±1.7) was found in abnormal WBC counts group I and III in comparison with normal WBC counts group II (7.37±2.67).…”