TISSUE-SPECIFIC CYTOKINE PRODUCTION DURING EXPERIMENTAL ACUTE-PANCREATITIS - A PROBABLE MECHANISM FOR DISTANT ORGAN DYSFUNCTION

Our purpose was to determine if cytokines are produced systemically du ring acute pancreatitis. Proinflammatory cytokines are elevated during acute pancreatitis and have been implicated in the progression of pan creatitis-associated multiple organ dysfunction. Whether these mediato rs are produced within all tissues or very few specific organs is not known. Edematous pancreatitis was induced in adult male mice by IP inj ection of cerulein. Necrotizing pancreatitis was induced in young fema le mice by feeding a choline-deficient, ethionine supplemented diet. A nimals were sacrificed as pancreatitis worsened, with multiple organs prepared for tissue mRNA and protein analysis by RT-PCR and immunoblot ting. Pancreatitis severity was established by histologic grading and serum amylase and lipase. There was no cytokine mRNA or protein detect able prior to the induction of pancreatitis. Tumor necrosis factor-alp ha (TNF-alpha) and interleukin-l-beta (IL-1 beta) mRNA and protein wer e detected within the pancreas early in the course of pancreatitis in both models, coinciding with the development of hyperamylasemia (both P < 0.001). Interleukin-6 was produced in the pancreas after pancreati tis was more fully developed (P < 0.001). IL-1 beta and TNF-alpha were subsequently produced in large amounts in lung, liver, and spleen but never within kidney, cardiac muscle, or skeletal muscle. A significan t delay between pancreatic and distant organ cytokine production was a lways observed. It is concluded that proinflammatory cytokines are pro duced within the pancreas and within organs known to develop dysfuncti on during severe pancreatitis. Cytokine production is tissue specific, correlates with disease severity, and occurs within the pancreas firs t and subsequently within distant organs.