Immunmodulation im Cholesteatom

Zusammenfassung

Einleitung Die Ätiopathogenese der chronischen Otitis media epitympanalis bzw. des Cholesteatoms und ihr proliferierender destruierender Verlauf mit möglichen Komplikationen wie Destruktion der knöchernen Strukturen mit Hörverlust, vestibulärer Dysfunktion, Gesichtsnervenlähmung und intrakraniellen Komplikationen sind immer noch ungeklärt. Die Therapie der Wahl ist nach wie vor die operative Sanierung. Aktuelle Studien befassen sich immer mehr mit dem angeborenen Immunsystem.

Methoden Unsere Untersuchungen erfolgten im Mausmodell an WT-Mäusen und immundefizienten KO-Mäusen sowie an Gewebeproben vom Cholesteatom, gesunder Gehörgangshaut und gesunder Mittelohrschleimhaut, die während sanierenden Ohroperationen entnommen wurden. Die Expressionsanalysen erfolgten auf Gen- und Proteinebene mit TNF als Major Target zur Therapieevaluation. Mittels TUNEL-Färbung und Immunhistochemie an Kryoschnitten wurde die Apoptose-Rate durch TNF bestimmt.

Ergebnisse Das ungerichtet-expansive Cholesteatomwachstum zeigt ein immunmodulatorisches Profil mit Hoch- und Runterregulation von verschiedenen Gen-Netzwerken, vor allem Molekülen der TNF-Down- und -Upstream-Signalwege. Dabei wird TNF sowohl inflammatorisch als auch apoptotisch moduliert und eignet sich als möglicher Therapieansatz in verschiedenen Modellen.

Schlussfolgerungen Es gibt Hinweise auf eine immunmodulatorische Regulation im Cholesteatom.

Abstract

Introduction The etiopathogenesis of chronic otitis media epitympanalis/cholesteatoma and its proliferative destructive course with possible complications such as destruction of bony structures with hearing loss, vestibular dysfunction, facial nerve paralysis and intracranial complications are still unexplained. Surgery is still the way to go. New studies are increasingly looking at the innate immune system.

Methods Our studies were carried out in a mouse model in WT mice and immundeficient KO-mice, as well as in cholesteatoma and healthy ear canal skin and middle ear tissue, which was removed during ear surgery. The expression analyses were carried out at the gene and protein level using TNF as the major target for therapy evaluation. By means of TUNEL staining and immunohistochemistry the level of apoptosis was evaluated.

Results The uncontrolled undirected cholesteatoma growth shows an immunomodulatory profile with up and down-regulation of various gene networks, especially those involved in TNF downstream and upstream signaling pathways. TNF in cholesteatoma is modulated both inflammatorily and apoptotically and therefore is suitable as a possible therapeutic approach in various models.

Conclusions Cholesteatoma might be immunomodulatory regulated.

Schlüsselwörter

Cholesteatom - Immunsystem - Apoptose - TNF - Immuntherapie

Keywords

Cholesteatoma - Innate Immunity - Apoptosis - TNF - Immunotherapy

Publication History

Received: 02 March 2021

Accepted after revision: 21 May 2021

Article published online:
07 July 2021

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