title: Evidence for an unknown component of pancreatic ascites that induces adult respiratory distress syndrome through an interleukin-1 and tumor necrosis factor-dependent mechanism.
abstract: BACKGROUND
  The development of acute respiratory distress syndrome (ARDS) during acute pancreatitis is associated with interleukin (IL)-1 and tumor necrosis factor (TNF) gene expression within the pulmonary parenchyma. Although activated pancreatic enzymes have been thought to mediate pancreatitis-induced ARDS, they are not capable of inducing cytokine production in vitro. We hypothesized that IL-1 and TNF production in the lungs is essential to the development of ARDS and is induced by a mediator released from the inflamed pancreas.
  
  
  METHODS
  Pancreatic ascites was obtained from rats after induction of bile-salt pancreatitis, cultured, and assayed for IL-1, TNF, IL-6, IL-8, IL-10, interferon-gamma, and endotoxin. Sterile, cytokine-free ascites or saline (control) was subsequently administered intravenously (20 ml/kg) to healthy rats and to IL-1 R1 or TNF R1 knockout mice.
  
  
  RESULTS
  Animals administered intravenous ascites had a 30-fold rise in pulmonary IL-1 and TNF mRNA, as well as increased alveolar leukocytes and protein. Knockout animals devoid of active IL-1 or TNF receptors failed to develop increased alveolar protein or leukocytes.
  
  
  CONCLUSIONS
  A component of pancreatic ascites other than activated enzymes, bacteria, or inflammatory cytokines is capable of inducing ARDS in healthy animals. The mechanism appears to be directly attributable to the activity of pulmonary IL-1 and TNF.
authors.affiliation: Department of Surgery, University of South Florida, Tampa 33612, USA.
authors.forename: W
authors.initials: W
authors.lastname: Denham
authors.forename: J
authors.initials: J
authors.lastname: Yang
authors.forename: J
authors.initials: J
authors.lastname: Norman
mesh_terms: D000208:Acute Disease; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D001201:Ascites / Q000276:immunology*; D001647:Bile Acids and Salts; D001685:Biological Factors / Q000096:biosynthesis*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000096:biosynthesis; D007375:Interleukin-1 / Q000096:biosynthesis*; D016753:Interleukin-10 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D008168:Lung / Q000276:immunology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010195:Pancreatitis / Q000276:immunology* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017472:Receptors, Interleukin-1 / Q000172:deficiency / Q000235:genetics; D018124:Receptors, Tumor Necrosis Factor / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I; D012128:Respiratory Distress Syndrome / Q000209:etiology / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D015703:Antigens, CD; D001647:Bile Acids and Salts; D001685:Biological Factors; D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D017472:Receptors, Interleukin-1; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma