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, produc ed by infiltrating neutrophils, and endogenous protease inhibitors. Ob jective: The aim of this study was to evaluate the role of recombinant alpha-1-antichymotrypsin (rACT P-3-P-3')), an endogenous serine prote ase inhibitor, in ameliorating lung injury associated with pancreatiti s. Design: Sprague-Dawley rats were randomly divided into control (sal ine infusion) and pancreatitis groups, which were treated immediately with saline or rACT P3-P3' (50 mg/kg body weight). Methods: Myeloperox idase (MPO) was employed as a monitor of neutrophil traffic in the lun g, and wet-dry lung weights as a measure of pulmonary endothelial perm eability. Lungs were also evaluated histologically. Results: Caerulein (5 mu g/kg body weight/h) induced pancreatitis in all animals, with a n increase in serum amylase from 1851+/-208IU (control) to 5198+/-924I U (pancreatitis), P<0.05. Pancreatitis caused a significant increase i n MPO activity (7.8+/-1.1 units compared with 2.08+/-0.5 units in cont rols, P<0.001) and wet-dry lung weight ratios (12.8+/-3.3 compared wit h 3.2+/-0.1 in controls, P<0.001), indicating significant pulmonary ne utrophil influx and microvascular leakage, respectively. These increas es in MPO activity and wet-dry ratios were decreased in the pancreatit is group treated with rACT P-3-P-3' (MPO 4.68+/-0.7 units, wet-dry rat io 4.2+/-0.5, P< 0.05 compared with the untreated pancreatitis group). Conclusion: These data support the hypothesis that deficient endogeno us protease inhibition may be responsible for the neutrophil-mediated lung injury observed in pancreatitis and suggest that there may be a t herapeutic role for recombinant protease inhibitors such as alpha-1-an tichymotrypsin.