Interleukin-6 and tumour necrosis factor alpha synthesized by cholesteatoma cells affect mucociliary function in the eustachian tube.

The aims of this study were to investigate the possible synthesis of IL-6 and TNF-alpha by cholesteatoma cells in culture and the effect of IL-6 and TNF-alpha produced by cultured cholesteatoma cells on the function of the mucociliary system in the tubotympanum. Cholesteatoma cells were collected from 10 patients, and the medium supernatants in which cholesteatoma cells or normal human epidermoid cells had been cultured for 48 h were collected. The concentrations of IL-6 and TNF-alpha in the supernatants were measured by enzyme-linked immunosorbent assays. The effect of the culture supernatants on ciliary activity was examined using an in vitro experimental system. The supernatants were injected into the tympanic cavities of guinea pigs, and mucociliary clearance time of the Eustachian tube was determined according to our dye transport technique 24 h after the intratympanic injection. Human cholesteatoma cells produced larger amounts of IL-6 and TNF-alpha than normal human epidermoid cells. The supernatants of cholesteatoma cells compromised ciliary activity and mucociliary clearance of the Eustachian tube in the guinea pigs. The effects of the supernatants of cholesteatoma cells on the ciliary activity and mucociliary clearance were correlated with the concentration of IL-6 and TNF-alpha in the supernatants. In conclusion, cholesteatoma cells can produce IL-6 and TNF-alpha, which are able to compromise the mucociliary function in the tubotympanum. IL-6 and TNF-alpha produced in middle ear cholesteatoma might aggravate the disease by the wide range of their biological activities on the mucociliary system, the proliferation of cholesteatoma cells and the bone metabolism.