EVIDENCE FOR AN UNKNOWN COMPONENT OF PANCREATIC ASCITES THAT INDUCES ADULT-RESPIRATORY-DISTRESS-SYNDROME THROUGH AN INTERLEUKIN-1 AND TUMORNECROSIS FACTOR-DEPENDENT MECHANISM

Background. The development of acute respiratory distress syndrome (AR DS) during acute pancreatitis is associated with interleukin (IL)-1 an d tumor necrosis factor (TNF) gene expression within the pulmonary par enchyma. Although activated pancreatic enzymes have been thought to me diate pancreatitis-induced ARDS, they are not capable of inducing cyto kine production in vitro. We hypothesized that IL-1 and TNF production in the lungs is essential to the development of ARDS and is induced b y a mediator released from the inflamed pancreas. Methods. Pancreatic ascites was obtained from rats after induction of bile-salt pancreatit is, cultured and assayed for IL-1, TNF, IL-6, IL-8, IL-10, interferon- gamma, and endotoxin. Sterile, cytokine-free ascites or saline (contro l) was subsequently administered intravenously (20 ml/kg) to healthy r ats and to IL-1 R1 or TNF R1 knockout mice. Results. Animals administe red intravenous ascites had a 30-fold rise in pulmonary IL-1 and TNF m RNA, as well as increased alveolar leukocytes and protein. Knockout an imals devoid of active IL-1 or TNF receptors failed to develop increas ed alveolar protein or leukocytes. Conclusions. A component of pancrea tic ascites other than activated enzymes, bacteria, or inflammatory cy tokines is capable of inducing ARDS in healthy animals. The mechanism appears to be directly attributable to the activity of pulmonary IL-1 and TNF.