Effect of endotoxin on cultured rat middle ear epithelium, rat meatal epidermis, and human keratinocytes.

Several factors seem to contribute to the series of events in the pathogenesis of otitis media and cholesteatoma. Endotoxin is likely to be one of these factors, since it has been found in human middle ear effusions and since injection of this substance into the middle ear, in animal experiments, gave rise to prominent reactions. Provoking of epithelial cells in vitro with endotoxin led to distinct cell responses that might be associated with cholesteatoma formation. In this study the effect of endotoxin on serially cultured rat middle ear epithelium, rat meatal epidermis, and human keratinocytes was investigated. Endotoxin strongly stimulated the proliferation of middle ear epithelium and human keratinocytes and inhibited that of meatal epidermis. Furthermore, endotoxin affected the morphology of the three types of tissue. Rat middle ear epithelium revealed epithelial cell tracks with interconnecting bridge-like structures protruding above the culture plane, whereas rat meatal epidermis showed increased terminal differentiation expressing large areas of blister-like structures detaching from the culture dish. Cross-linked envelope analysis of human keratinocytes showed an increased terminal differentiation that was morphologically confirmed but was not confirmed by cytokeratin analysis. The results of this study support the hypothesis that endotoxin may play an important role in the pathogenesis of otitis media and cholesteatoma.