Alpha-1-antichymotrypsin is an effective inhibitor of pancreatitis-induced lung injury

Background: Pancreatitis-induced adult respiratory distress syndrome (ARDS) may result from an imbalance between leucocyte proteases, produced by infiltrating neutrophils, and endogenous protease inhibitors. Objective: The aim of this study was to evaluate the role of recombinant alpha-1-antichymotrypsin (rACT P₃-P₃'), an endogenous serine protease inhibitor, in ameliorating lung injury associated with pancreatitis. Design: Sprague-Dawley rats were randomly divided into control (saline infusion) and pancreatitis groups, which were treated immediately with saline or rACT P₃-P₃' (50 mg/kg body weight). Methods: Myeloperoxidase (MPO) was employed as a monitor of neutrophil traffic in the lung, and wet-dry lung weights as a measure of pulmonary endothelial permeability. Lungs were also evaluated histologically. Results: Caerulein (5 μg/kg body weight/h) induced pancreatitis in all animals, with an increase in serum amylase from 1851 ± 208 IU (control) to 5198 ± 924 IU (pancreatitis), P < 0.05. Pancreatitis caused a significant increase in MPO activity (7.8 ± 1.1 units compared with 2.08 ± 0.5 units in controls, P < 0.001) and wet-dry lung weight ratios (12.8 ± 3.3 compared with 3.2 ± 0.1 in controls, P < 0.001), indicating significant pulmonary neutrophil influx and microvascular leakage, respectively. These increases in MPO activity and wet-dry ratios were decreased in the pancreatitis group treated with rACT P₃-P₃' (MPO 4.68 ± 0.7 units, wet-dry ratio 4.2 ± 0.5, P < 0.05 compared with the untreated pancreatitis group). Conclusion: These data support the hypothesis that deficient endogenous protease inhibition may be responsible for the neutrophil-mediated lung injury observed in pancreatitis and suggest that there may be a therapeutic role for recombinant protease inhibitors such as alpha-1-antichymotrypsin.