Inflammatory proteases in chronic otitis externa.
OBJECTIVE
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.


METHODS
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.
Antonelli
Patrick J
PJ
Department of Otolaryngology, University of Florida, Gainesville, Florida 32610-0264, USA. antonpj@ent.ufl.edu
Schultz
Gregory S
GS
Cantwell
John S
JS
Sundin
David J
DJ
Pemberton
Philip A
PA
Barr
Philip J
PJ
D002908:Chronic Disease; D004792:Enzyme Precursors / Q000032:analysis / Q000037:antagonists & inhibitors; D005260:Female; D006801:Humans; D006877:Hydroxamic Acids; D007211:Indoles / Q000494:pharmacology; D018836:Inflammation Mediators / Q000032:analysis*; D019272:Leukocyte Elastase / Q000032:analysis* / Q000037:antagonists & inhibitors; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000032:analysis; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000032:analysis*; D008875:Middle Aged; D010032:Otitis Externa / Q000201:enzymology*; D011446:Prospective Studies; D011480:Protease Inhibitors / Q000494:pharmacology; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D000515:alpha 1-Antitrypsin / Q000494:pharmacology
D004792:Enzyme Precursors; D006877:Hydroxamic Acids; D007211:Indoles; D018836:Inflammation Mediators; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D015842:Serine Proteinase Inhibitors; D000515:alpha 1-Antitrypsin; D019272:Leukocyte Elastase; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C119203:ilomastat