Alpha 1-Antitrypsin and Ilomastat Inhibit Inflammatory Proteases Present in Human Middle Ear Effusions
Autor: | Patrick J. Antonelli, Philip A. Pemberton, John S. Cantwell, Gregory S. Schultz, David J. Sundin, Philip J. Barr, Karen M. Kim |
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Rok vydání: | 2003 |
Předmět: |
Adult
Male Proteases Indoles Serine Proteinase Inhibitors Adolescent medicine.medical_treatment In Vitro Techniques Matrix Metalloproteinase Inhibitors Matrix metalloproteinase Hydroxamic Acids Otitis Media Suppurative Pathogenesis Recurrence medicine Humans Protease inhibitor (pharmacology) Metalloproteinase Protease Otitis Media with Effusion business.industry Elastase Matrix Metalloproteinases Matrix Metalloproteinase 9 Otorhinolaryngology Child Preschool alpha 1-Antitrypsin Chronic Disease Immunology Matrix Metalloproteinase 2 Female Inflammation Mediators Leukocyte Elastase business Ex vivo |
Zdroj: | The Laryngoscope. 113:1347-1351 |
ISSN: | 0023-852X |
Popis: | Objectives Proteases of both the serine and metalloproteinase families have been shown to play a role in the pathogenesis of otitis media (OM). Inhibitors of proteases from each of these families have been shown to beneficially impact disease progression in a number of related chronic inflammatory conditions, but their use has not been studied in OM. The purpose of this study was to assess the activity of the protease inhibitors recombinant alpha 1-antitrypsin (rAAT) and ilomastat on inflammatory proteases present in human middle ear effusions (MEEs), with a view to their potential utility in the treatment of OM. Study Design Prospective and ex vivo. Methods MEEs were collected from 100 patients presenting for middle ear surgery, most commonly tympanostomy tube placement or treatment of acute posttympanostomy otorrhea (APTO). MEEs were analyzed for the presence of matrix metalloproteinases (MMPs) and human neutrophil elastase (HNE) and the inhibitory activity of rAAT and ilomastat on these proteases, respectively. Results MMP levels were highest in APTO, and HNE was highest in chronic suppurative OM and APTO. High levels of MMP and HNE (>3 mAU/min) were found in 52% and 37% of MEEs, respectively. Ilomastat and rAAT demonstrated significant inhibition of MMP and HNE activity (>30% reduction), respectively, in 80% and 82% of MEEs with high levels of activity. Conclusions Proteases are commonly found in OM. Ilomastat and rAAT are potent inhibitors of proteases in MEEs across a wide range of OM in humans. Investigation into the potential therapeutic benefits of these protease inhibitors is warranted. |
Databáze: | OpenAIRE |
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