The significance of protease inhibitors in the pathogenesis of otitis media with effusion.

Concentration of alpha 1-antitrypsin (alpha 1-AT), alpha 1-antichymotrypsin (alpha 1-AChyT), inter-alpha-trypsin inhibitor (I-alpha-I), and alpha 2-macroglobulin (alpha 2-M) was measured in 27 serous middle ear effusions (MEEs) from 24 adult patients. The presence of protease-inhibitor complex was analyzed by crossed immunoelectrophoresis (CIEP). Mean concentration of alpha 1-AT was 361 +/- 90.0 mg/dl and was higher than that of other inhibitors: alpha 1-AChyT, 80.6 +/- 40.7; I-alpha-I, 21.3 +/- 21.5; alpha 2-M, 59.5 +/- 57.1. Molar concentration of alpha 2-M was the lowest. Most of alpha 1-AT and alpha 1-AChyT in MEEs were unsaturated; free inhibitors. Alpha-1-AT could be saturated by trypsin and elastase immediately, and only alpha 2-M could be saturated by papain (classical thiol protease). Serous MEEs have high anti-trypsin activity attributed to mainly free alpha 1-AT. Since level of alpha 2-M was very low, lysosomal thiol proteases could be one of the major proteases inducing proteolytic damage to middle ear mucosa.