Objective: To develop an animal model for testing efficacy of anti-inflamma
tory drugs designed to treat external ear canal (EAC) disease. Methods: His
tological and morphometric methods were used to characterize EAC inflammati
on produced by topical application of tetradecanoylphorbol acetate (TPA) in
mice. The effects of both single and repeated TPA applications were studie
d. A treatment trial was performed to evaluate the effects of a ciprofloxac
in/hydrocortisone suspension on TPA-induced EAC inflammation. In 10 animals
, two bilateral applications of TPA were made, spaced 24 hours apart. Immed
iately after the second TPA application, otic suspension was applied unilat
erally four times over a 48-hour period. The contralateral EACs were left u
ntreated to provide TPA-only controls. Results: Twenty-four hours after a s
ingle TPA application, EAC skin showed polymorphonuclear (PMN) leukocyte in
filtration, vascular dilation, and thickening of the dermis and epidermis,
Dermal and epidermal thickening were more pronounced after two TPA applicat
ions and PMN leukocyte infiltration remained high 48 hours after a second T
PA placement. After treatment with the otic suspension, PMN leukocyte count
s were reduced by an average of 76% relative to EACs that received TPA only
. There was also statistically significant reduction of dermal swelling and
a trend toward reduced epidermal thickness. Vascular dilation was clearly
reduced as well. EACs that received four applications of the suspension alo
ne show ed no adverse effects compared with those that received saline. Con
clusion: TPA-induced inflammation of the mouse EAC provides a suitable mode
l for testing the therapeutic efficacy of anti-inflammatory agents being co
nsidered for clinical use.