Characterization of cytokines present in middle ear effusions

Abstract

Retention of inflammatory mediators and cells in the middle ear cleft during chronic otitis media with effusion (COME), results in ongoing inflammation with the potential for pathologic changes and hearing loss. Cytokines are glycoproteins produced by macrophages and other cells. Activities of cytokines include fever production, osteoclast, fibroblast, phagocyte and cytotoxic cell activation, regulation of antibody formation, and inhibition of cartilage, bone and endothelial cell growth. Using enzyme-linked immunospecific assays we measured levels of six cytokines in middle ear effusions (MEE) from children with COME. Significant levels of four cytokines: interleukin-1-beta (greater than 50 pg/ml), interleukin-2 (greater than 300 pg/ml), tumor necrosis factor-alpha (greater than 40 pg/ml), and gamma-interferon (greater than 6.25 pg/ml) were found in 51%, 54%, 63%, and 19% of MEE, respectively. In contrast, levels of a fifth cytokine, granulocyte-macrophage colony-stimulating factor, and a sixth cytokine, interleukin-4, were undetectable. Age was observed to have a significant effect on the levels of specific cytokines. Interleukin-1 (IL-1) correlated inversely (P less than .02) with age such that the younger the child, the higher the level of IL-1 in MEE. Tumor necrosis factor-alpha (TNF) correlated directly (P less than .005) with age such that the older the child, the higher the level of TNF in MEE. Children undergoing tympanostomy on multiple occasions had average MEE TNF levels (234.2 +/- 109.1 pg/mg total protein) that were nearly 14 times higher (P less than .005) than those from children undergoing their first tympanostomy (16.9 +/- 3.0 pg/mg total protein). Thus IL-1 correlated with the early stages of COME, while TNF correlated with persistence of disease. The presence of these cytokines in MEE may be responsible for the mucosal damage, bone erosion, fibrosis, and resulting hearing loss seen in some cases of COME.

Functional and Molecular Expression of Epithelial Sodium Channels in Cultured Human Endolymphatic Sac Epithelial Cells

“…Interleukin 1A (IL-1A) is one of the important cytokines in the inflammatory process. The level of IL-1A in endolymph increases after noise exposure (12) or during otitis media (13,14). It is also well known that sensory neural hearing loss and M Ménière's disease are aggravated during systemic infection (15Y17).…”

Role of Macrophage Migration Inhibitory Factor in Otitis Media with Effusion in Adults

“…In children, many studies have demonstrated the involvement of immune reactions and/or eustachian tube dysfunction induced by bacterial infections in the middle ear and/or nasopharynx in the pathogenesis of OME (4,10,13,14,16,30,31). To date, several inflammatory cytokines such as interleukin 1 (IL-1), IL-2, IL-6, IL-8, and tumor necrosis factor alpha (TNF-␣) are observed in middle ear effusions (MEEs) (13,30,31). In addition, bacterial DNAs and components such as endotoxins are also detected in MEEs, whereas bacterial culture from MEEs is often negative (4,10,16).…”

The Relation between Tympanostomy Tube Otorrhea and Types of Immune Cells in Middle Ear Effusion in Children with Otitis Media with Effusion

“…88 The analysis of peripheral blood immunologic pattern in patients with persistent middle ear effusions 89,90 showed the following: (1) the number of CD4…”