Pancreatic elastase activates pulmonary nuclear factor kappa B and inhibitory kappa B, mimicking pancreatitis-associated adult respiratory distress syndrome

Background. Select pancreatic enzymes, primarily elastase, precipitate pulmonary injury similar to pancreatitis-associated adult respiratory distress syndrome and stimulate leukocyte cytokine production in vitro via nuclear factor kappa B (NF-kappa B) activation. This study explores the effect of systemic pancreatic enzymes on pulmonary NF-kappa B and inhibitory Kappa B (I kappa B) proteins and their rob in enzyme-induced pulmonary injury. Methods. Mice received pancreatic elastase, amylase, lipase, or trypsin intraperitoneally. Bronchoalveolar lavage I kappa B alpha/l kappa B beta proteins were measured by immunoblot. Pulmonary, NF-kappa B activation, tumor necrosis factor (TNF) gene expression, and neutrophil infiltration (myeloperoxidase) were deter milled and myeloperoxidase experiments repeated in p55 TNF receptor-deficient (TNF KO) animals. Additional animals received pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-kappa B activation, and TNF protein and pulmonary microvascular permeability were measured after elastase administration. Results. Pancreatic elastase induced pulmonary I kappa B alpha/I kappa B beta degradation (30 minutes), NF-kappa B activation (60 minutes), and TNF gene expression (60 minutes) with subsequent neutrophilic inflammation (4 hours) and microvascular leakage (24 hours), whereas amylase, lipase, and trypsin did not. Furthermore, lung injury was markedly reduced in TNF KO animals and PDTC significantly attenuated TNF production and pulmonary microvascular leakage. Conclusions. Pancreatic elastase induces cytokine-mediated lung injury and this pathway involves the NF-kappa B second messenger system, further supporting elastase as a factor linking pancreatic inflammation to systemic illness during severe acute pancreatitis.