EFFECT OF RECOMBINANT PLATELET-ACTIVATING-FACTOR ACETYLHYDROLASE ON 2MODELS OF EXPERIMENTAL ACUTE-PANCREATITIS

Background & Aims: Recent reports suggest that platelet-activating fac tor (PAF) plays a role in pancreatitis and pancreatitis-associated lun g injury. In this study, the effects on these processes of termination of PAF action by recombinant PAF-acetylhydrolase (rPAF-AH) were inves tigated. Methods: Rats were given rPAF-AH and then infused with a supr amaximally stimulating dose of cerulein to induce mild pancreatitis. O possums underwent biliopancreatic duct ligation to induce severe pancr eatitis, and rPAF-AH administration was begun 2 days later. Results: I n mild, secretagogue-induced pancreatitis, rPAF-AH given before the ce rulein reduced hyperamylasemia, acinar cell vacuolization, and pancrea tic inflammation but did not alter pancreatic edema or pulmonary micro vascular permeability. In severe, biliopancreatic duct ligation-induce d pancreatitis, rPAF-AH delayed and reduced the extent of inflammation and acinar cell injury/necrosis and completely prevented lung injury even though the rPAF-AH administration was begun after the onset of pa ncreatitis. Conclusions: PAF plays an important role in the regulation of pancreatic injury but not pancreatic edema or increased pulmonary microvascular permeability in mild, secretagogue-induced pancreatitis. PAF plays a critical role in the regulation of progression of pancrea tic injury and mediation of pancreatitis-associated lung injury in sev ere biliary pancreatitis, Amelioration of pancreatitis and prevention of pancreatitis-associated lung injury can be achieved with rPAF-AH ev en if treatment is begun after pancreatitis is established.