Tumor necrosis factor alpha in middle ear cholesteatoma and its effect on keratinocytes in vitro.

Tumor necrosis factor alpha (TNF-alpha) was found in human middle ear cholesteatoma tissues by the immunoperoxidase method using rabbit anti human TNF-alpha immunoglobulin G. It appeared to be localized in the epithelium and connective tissue of cholesteatomas studied, particularly on basal and spinous cells, and macrophages. The epithelium of normal external ear canal skin was lightly stained, but the staining was much weaker than that of the cholesteatomas observed. In vitro, recombinant mouse TNF-alpha stimulated proliferation, protein synthesis, and terminal differentiation of basal keratinocytes. These stimulatory effects were blocked by the anti-TNF-alpha immunoglobulin G, which by itself had no effect on basal keratinocytes. These findings suggest that TNF-alpha plays an important role in the development of cholesteatomas seen clinically.