Inflammatory Proteases in Chronic Otitis Externa

Abstract

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. Prospective and ex vivo. 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. 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. 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.