Acquired cholesteatoma is associated with an intense inflammatory reac
tion with resultant tissue and bone destruction, Cytokines are molecul
es released by inflammatory cells at the site of infection and are pot
ent mediators of inflammation and the immune response. Five cytokines,
tumor necrosis factor-alpha, transforming growth factor-beta 1 and 2,
and interleukin-1 and 6, were immunolocalized in human cholesteatoma
epithelium and subepithelial stroma, with greater intensity of stainin
g compared with noninflamed external auditory canal skin, Increased in
terleukin-6 activity in cholesteatoma epithelium and stroma correlated
significantly with the presence of ossicular and bony erosion and gra
nulation tissue noted intraoperatively. Transforming growth factor-bet
a 2 activity in cholesteatoma epithelium correlated significantly with
bony erosion at surgery. Additionally, transforming growth factor-bet
a 1 activity in cholesteatoma epithelium correlated significantly with
increased length of disease, Tumor necrosis factor-alpha, interleukin
-1, and interleukin-6 appear to be involved in the inflammation and re
sultant remodeling associated with cholesteatoma. We hypothesized a pr
otective function of transforming growth factor-beta 1 and 2 in the pr
esence of cholesteatoma, The antiinflammatory and osteoclast and kerat
inocyte inhibitory actions of the transforming growth factor-beta s co
uld potentially slow the proliferation and resultant tissue destructiv
eness associated with cholesteatoma.