Role of cytokines and Th17/Tregs imbalance in the pathogenesis of otitis media with effusion. Modulation of Notch1/Hes1/mTORC1/S6k1 signalling pathway underlies the protective effect of astaxanthin.

Otitis media with effusion (OME) is a recurrent middle ear inflammatory condition. It may be complicated by acquired hearing loss and speech impairment especially in children. Accordingly, the current study aimed to assess the role of cytokines and the imbalance of Th17/Tregs in the pathogenesis of OME. Additionally, the protective effect of astaxanthin and its mechanisms related to Notch1/ Hes1/mTORC1/S6K1 signalling were investigated. METHODS: Forty-eight children were grouped as follow: G1: control healthy group G2: acute otitis media (AOM) group, G3: OME group. In the lipopolysaccharide (LPS) induced OME rat model, 15 rats were randomised into: G1: normal control group, G2: LPS group, and G3: astaxanthin treated group. RESULTS: Biochemical analysis of the children's peripheral blood samples showed that IL1ß, IL-2, IL-4, IL-6, IL-17, and IL-23 were significantly elevated, while TGF-ß was significantly decreased in AOM and OME patients (group 2 and 3). In the LPS- induced OME rat model, astaxanthin treatment resulted in suppression of IL-17, IL-6, TNF-α, Muc5A, TFF3, NICD, Hes1, mTORC1, and S6K1 in rat middle ear mucosa. Furthermore, astaxanthin significantly downregulated RORγ while upregulating FoxP3 and restored the balance between Th17/Tregs. Moreover, astaxanthin improved the histopathological picture of the inflamed middle ear mucosa. CONCLUSIONS: Proinflammatory cytokines as well as Th17/Tregs imbalance play a crucial role in the pathogenesis of AOM and OME. Additionally, astaxanthin alleviated LPS- induced OME in rats through suppression of Notch1/ Hes1/mTORC1/S6K1 pathway, and regulation of Th17/Tregs.

Squamous Metaplasia and BCL-6 in Pediatric Adenoid Accompanied by Otitis Media with Effusion

PURPOSE: Deterioration of local immunity in the adenoids may make them vulnerable to infection by microorganisms, resulting in otitis media with effusion. To determine the factors associated with this condition, we evaluated adenoid size, mucosal barrier, squamous changes of ciliated epithelium, IgA secretion, and BCL-6 expression in adenoids. MATERIALS AND METHODS: Seventeen children diagnosed with otitis media with effusion (OME group) and 20 children without any history of OME (control group) were enrolled. Their adenoids were sized by lateral view X-ray and stained with hematoxylin and eosin to detect squamous metaplasia. The adenoids were also stained with cytokeratin to evaluate mucosal barriers, and with anti- IgA antibody and anti- BCL-6 antibody to determine expression of IgA and BCL-6. RESULTS: The OME group showed greater incidence of squamous metaplasia, fewer ciliated cells, and lower expression of BCL-6 (p 0.05). IgA secretion and adenoid size were the same for the OME and the control groups. CONCLUSION: These results suggest that increased squamous metaplasia and lower BCL-6 expression in adenoids may be associated with increased susceptibility to OME.

Lipoperoxidación en otorreas del oído medio como marcador de infección. Aplicación clínica / Lipid peroxides in middle ear discharge as a marker of infection. Clinical application

Si la generación de radicales libres derivados del oxígeno es condición fisiopatológica en las infecciones del oído medio, como ha sido recientemente publicado, la demostración de las consecuencias oxidativas por estos radicales en los exudados del oído medio pueden suponer una medida objetiva, accesible, sencilla y rápida de cuantificar la intensidad de la agresión sufrida por su mucosa. Así, en las muestras supuradas obtenidas de oídos con otitis media aguda (n = 17), otitis media crónica colesteatomatosa (n = 17), otorrea crónica no colesteatomatosa (n = 10) y otitis media secretora (n = 15) se cuantificó mediante un ensayo enzimático colorimétrico la actividad lipoperoxidante derivada del daño por los radicales superóxido e hidroxilo durante la infección. En las tres primeras entidades los valores oscilaron entre 575 y 650 nmoles/mg de exudado, frente a 67 nmoles/mg en otitis secretora, diferencias estadísticamente significativas. Las otitis infecciosas por lo tanto evidencian signos derivados de un metabolismo oxidativo exacerbado que no se observa en la otitis media secretora, cuya cuantificación permite monitorizar la evolución de un episodio, prevenir las recidivas o reinfecciones y valorar la respuesta a nuevas alternativas terapéuticas de la otitis supurada como los antioxidantes en aplicación tópica (AU)

If the generation of free oxygen radicals is a pathophysiological finding in middle-ear infections, as has been reported, demonstration of the oxidative consequences of free radicals in middle-ear exudates may be a quick, simple, objective and accessible test for quantifying the degree of mucosal injury. Therefore, samples of the discharge fluid from cases of acute otitis media (n = 17), cholesteatoma (n = 17), chronic discharge in the absence of cholesteatoma (n = 10), and secretory otitis media (n = 15) were tested using an enzymatic colorimetric assay for lipid peroxide levels due to superoxide and hydroxyl radicals during infection. Lipid peroxide levels in acute otitis media, cholesteatoma, and chronic discharge without cholesteatoma ranged from 575 to 650 nmol/mg of exudate, and was 67 nmol/mg in secretory otitis media, which were statistically significant findings. Infectious otitis media showed findings secondary to increased oxidative metabolism, but not secretory otitis media. Measurement of this oxidative metabolism could serve to monitor the evolution of episodes, as well as to detect relapse or reinfection, and to evaluate response to new therapeutic options for suppurative otitis, such as topical antioxidants (AU)