An animal model for external ear canal inflammation.
OBJECTIVE
To develop an animal model for testing efficacy of anti-inflammatory drugs designed to treat external ear canal (EAC) disease.


METHODS
Histological and morphometric methods were used to characterize EAC inflammation produced by topical application of tetradecanoylphorbol acetate (TPA) in mice. The effects of both single and repeated TPA applications were studied. A treatment trial was performed to evaluate the effects of a ciprofloxacin/hydrocortisone suspension on TPA-induced EAC inflammation. In 10 animals, two bilateral applications of TPA were made, spaced 24 hours apart. Immediately after the second TPA application, otic suspension was applied unilaterally four times over a 48-hour period. The contralateral EACs were left untreated to provide TPA-only controls.


RESULTS
Twenty-four hours after a single TPA application, EAC skin showed polymorphonuclear (PMN) leukocyte infiltration, vascular dilation, and thickening of the dermis and epidermis. Dermal and epidermal thickening were more pronounced after two TPA applications and PMN leukocyte infiltration remained high 48 hours after a second TPA placement. After treatment with the otic suspension, PMN leukocyte counts 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 alone showed no adverse effects compared with those that received saline.


CONCLUSIONS
TPA-induced inflammation of the mouse EAC provides a suitable model for testing the therapeutic efficacy of anti-inflammatory agents being considered for clinical use.
Wright
C G
CG
Department of Otolaryngology--Head and Neck Surgery, University of Texas Southwestern Medical Center, Dallas 75235-9035, USA.
Pawlowski
K S
KS
Roland
P S
PS
Meyerhoff
W L
WL
D000287:Administration, Topical; D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002939:Ciprofloxacin / Q000494:pharmacology / Q000627:therapeutic use*; D020405:Dermis / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D004424:Ear Canal / Q000473:pathology; D004817:Epidermis / Q000187:drug effects / Q000473:pathology; D005260:Female; D006854:Hydrocortisone / Q000494:pharmacology / Q000627:therapeutic use*; D007958:Leukocyte Count / Q000187:drug effects; D051379:Mice; D008809:Mice, Inbred C3H; D010032:Otitis Externa / Q000188:drug therapy*; D013535:Suspensions
D000890:Anti-Infective Agents; D000893:Anti-Inflammatory Agents; D013535:Suspensions; D002939:Ciprofloxacin; D006854:Hydrocortisone