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.