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Updated: Aug 11, 2026
A Comparative Study of Drug Delivery Methods Targeted to the Mouse Inner Ear: Bullostomy Versus Transtympanic Injection
Published on: March 8, 2017
Edema and cell infiltration in the phorbol ester-treated mouse ear are temporally separate and can be differentially
L M De Young1, J B Kheifets, S J Ballaron
1Department of Inflammation Biology, Syntex Research, Palo Alto, CA 94304.
Abstract:
The temporal patterns of edema and accumulation of the PMN marker enzyme, myeloperoxidase (MPO), were examined following application of tetradecanoylphorbol acetate (TPA) to mouse ears. After application of 2.5 micrograms TPA, edema peaked at 6 hr, while MPO activity peaked at 24 hr. Pharmacological agents with defined mechanisms of action, delivered orally or topically, were assessed for effects on these responses. For oral administration, compounds were delivered 1 hr before and 6 hr after TPA and for topical administration compounds were delivered at 15 min and 6 hr after TPA. Topical and oral corticosteroids inhibited both edema and MPO accumulation. Cyclooxygenase and lipoxygenase inhibitors were very effective against MPO accumulation but were either inactive or moderately active vs edema. Anti-histamine/anti-serotonin agents had little effect on edema, but could inhibit or exacerbate MPO accumulation depending on dose and route of administration. Topically applied histamine itself did not effect TPA-induced edema, but markedly suppressed MPO accumulation. Acetone, the vehicle, when topically applied between 0.5 and 2 hr after TPA inhibited MPO accumulation by 60-80%, but had little effect on edema. Acetone applied before 0.5 hr or after 2 hr had no effect on either parameter. These results indicate that in the TPA-induced ear inflammation model the MPO response at 24 hr may be a useful additional indicator of drug activity.
Insights
This study shows that measuring myeloperoxidase (MPO) activity 24 hours after TPA application in mouse ears can help evaluate anti-inflammatory drugs. Corticosteroids and certain enzyme inhibitors effectively reduced MPO levels.
Area of Science:
- Pharmacology
- Inflammation Research
- Drug Discovery
Background:
- Tetradecanoylphorbol acetate (TPA) is a common agent used to induce inflammation in mouse ear models.
- Edema and neutrophil infiltration (indicated by myeloperoxidase (MPO) activity) are key inflammatory responses.
- Understanding the temporal dynamics of these responses is crucial for evaluating anti-inflammatory agents.
Purpose of the Study:
- To investigate the temporal relationship between edema and MPO accumulation following TPA application.
- To assess the efficacy of various pharmacological agents in modulating TPA-induced inflammation.
- To determine if MPO activity can serve as a reliable indicator for drug activity in this model.
Main Methods:
- TPA was applied to mouse ears, and edema and MPO activity were measured over time.
- Various anti-inflammatory drugs, including corticosteroids, cyclooxygenase/lipoxygenase inhibitors, and antihistamines/anti-serotonin agents, were administered orally or topically.
- The effects of these agents on edema and MPO accumulation were quantified.
Main Results:
- Edema peaked at 6 hours, while MPO activity peaked at 24 hours post-TPA application.
- Topical and oral corticosteroids effectively reduced both edema and MPO levels.
- Enzyme inhibitors targeted MPO accumulation more effectively than edema, while antihistamines showed variable effects.
- Acetone, the vehicle, transiently inhibited MPO accumulation when applied within a specific timeframe.
Conclusions:
- The 24-hour MPO response in the TPA-induced ear inflammation model is a valuable secondary marker for assessing drug efficacy.
- Different classes of anti-inflammatory drugs exhibit distinct effects on edema and MPO accumulation.
- This model provides insights into the mechanisms of inflammation and potential therapeutic interventions.
