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Published on: November 1, 2024
Inflammatory proteases in chronic otitis externa
Patrick J Antonelli1, Gregory S Schultz, John S Cantwell
1Department of Otolaryngology, University of Florida, Gainesville, Florida 32610-0264, USA. antonpj@ent.ufl.edu
Objectives:
Proteases are known to contribute to the pathogenesis of chronic inflammatory skin conditions such as atopic dermatitis and psoriasis. Inhibition of these proteases has shown promise in the treatment of these skin conditions. The purpose of this study was to measure the matrix metalloproteinases (MMP) and human neutrophil elastase (HNE) activities in chronic otitis externa (COE) and to determine whether administration of protease inhibitors recombinant alpha 1-antitrypsin (rAAT) and ilomastat might reduce these protease activities.
Study Design:
Prospective and ex vivo.
Methods:
Twenty-five ear canals with COE and 34 with no pathology (i.e., controls) were debrided and filled with saline. After a tragal pump and 1 to 2 minutes, the washes were collected and analyzed for MMP and HNE activities and the inhibitory activity of rAAT and ilomastat on these proteases, respectively.
Results:
MMP and HNE levels were significantly higher (P = .0057 and .0112) in ears with COE than normal ears. MMP activity greater than 3 mAU/minute was observed in 30% of COE and 0% of controls (P = .0270). HNE activity greater than 3 mAU/minute was found in 77% of COE versus 7% of controls (P < .0001). Ilomastat and rAAT inhibited 60% of MMP and 98% of HNE activity, respectively, in COE ears.
Conclusions:
Elevated levels of proteases found in COE, MMP, and HNE may be inhibited with ilomastat and rAAT. The therapeutic potential of these protease inhibitors warrants investigation.
Insights
Matrix metalloproteinases (MMP) and human neutrophil elastase (HNE) are elevated in chronic otitis externa (COE). Protease inhibitors ilomastat and recombinant alpha 1-antitrypsin (rAAT) show potential for treating COE.
Area of Science:
- Otolaryngology
- Dermatology
- Biochemistry
Background:
- Proteases, including matrix metalloproteinases (MMP) and human neutrophil elastase (HNE), are implicated in chronic inflammatory skin conditions.
- Inhibiting these proteases has shown therapeutic promise for skin diseases.
Purpose of the Study:
- To quantify MMP and HNE activity in chronic otitis externa (COE).
- To assess the efficacy of protease inhibitors, recombinant alpha 1-antitrypsin (rAAT) and ilomastat, in reducing MMP and HNE activity in COE.
Main Methods:
- A prospective, ex vivo study involving 25 ears with COE and 34 control ears.
- Ear canal washes were collected and analyzed for MMP and HNE activities.
- Inhibitory effects of rAAT and ilomastat were evaluated.
Main Results:
- MMP and HNE levels were significantly higher in COE ears compared to controls (P = .0057 and .0112, respectively).
- Elevated MMP activity (>3 mAU/minute) was found in 30% of COE cases versus 0% of controls (P = .0270).
- Significantly higher HNE activity (>3 mAU/minute) was observed in 77% of COE cases compared to 7% of controls (P < .0001).
- Ilomastat inhibited 60% of MMP activity, and rAAT inhibited 98% of HNE activity in COE ears.
Conclusions:
- Chronic otitis externa (COE) exhibits elevated levels of MMP and HNE proteases.
- The protease inhibitors ilomastat and rAAT effectively reduced MMP and HNE activity, respectively, in COE.
- Further investigation into the therapeutic potential of these protease inhibitors for COE is warranted.
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