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Inflammatory proteases in chronic otitis media externa

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 metallopr...

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Bibliographic Details
Published in:Otolaryngology-head and neck surgery 2004-08, Vol.131 (2), p.P262-P262
Main Authors: Antonelli, Patrick J, Schultz, Gregory S, Cantwell, John S, Sundin, David J, Pemberton, Philip A, Barr, Philip J
Format: Article
Language:English
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Summary: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 if addition of the serine protease inhibitor, recombinant alpha 1-antitrypsin (rAAT), and the MMP inhibitor, ilomastat, might reduce these protease activities. Methods: Twenty-four ear canals with COE and 25 with no pathology (ie, controls) were debrided and filled with saline. After a tragal pump and 12 minutes dwell time, the washes were collected. MMP and HNE activities in the washings were measured using synthetic colorometric substrates selective for MMPs and HNE, and the inhibitions by rAAT and ilomastat were determined. Results: MMP and HNE levels were significantly higher ( P = 0.0057 and 0.0112) in ears with COE than normal ears. Furthermore, MMP activity > 3 mAU/min was observed in 30% of COE and 0% of controls ( P = 0.0270). HNE activity >3 mAU/min was found in 77% of COE vs 7% of controls ( P < 0.0001). Ilomastat and rAAT inhibited 60% of MMP and 98% of HNE activity, respectively, in COE ears. Conclusion: 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.
ISSN:0194-5998
1097-6817
DOI:10.1016/j.otohns.2004.06.541