PMID- 9286248 OWN - NLM STAT- MEDLINE DCOM- 19970925 LR - 20190721 IS - 0163-2116 (Print) IS - 0163-2116 (Linking) VI - 42 IP - 8 DP - 1997 Aug TI - Tissue-specific cytokine production during experimental acute pancreatitis. A probable mechanism for distant organ dysfunction. PG - 1783-8 AB - Our purpose was to determine if cytokines are produced systemically during acute pancreatitis. Proinflammatory cytokines are elevated during acute pancreatitis and have been implicated in the progression of pancreatitis-associated multiple organ dysfunction. Whether these mediators are produced within all tissues or very few specific organs is not known. Edematous pancreatitis was induced in adult male mice by IP injection of cerulein. Necrotizing pancreatitis was induced in young female mice by feeding a choline-deficient, ethionine supplemented diet. Animals were sacrificed as pancreatitis worsened, with multiple organs prepared for tissue mRNA and protein analysis by RT-PCR and immunoblotting. Pancreatitis severity was established by histologic grading and serum amylase and lipase. There was no cytokine mRNA or protein detectable prior to the induction of pancreatitis. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1-beta (IL-1 beta) mRNA and protein were 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 pancreatitis 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 significant delay between pancreatic and distant organ cytokine production was always observed. It is concluded that proinflammatory cytokines are produced within the pancreas and within organs known to develop dysfunction during severe pancreatitis. Cytokine production is tissue specific, correlates with disease severity, and occurs within the pancreas first and subsequently within distant organs. FAU - Norman, J G AU - Norman JG AD - Department of Surgery, University of South Florida, Tampa 33612, USA. FAU - Fink, G W AU - Fink GW FAU - Denham, W AU - Denham W FAU - Yang, J AU - Yang J FAU - Carter, G AU - Carter G FAU - Sexton, C AU - Sexton C FAU - Falkner, J AU - Falkner J FAU - Gower, W R AU - Gower WR FAU - Franz, M G AU - Franz MG LA - eng PT - Journal Article PT - Research Support, U.S. Gov't, Non-P.H.S. PL - United States TA - Dig Dis Sci JT - Digestive diseases and sciences JID - 7902782 RN - 0 (Actins) RN - 0 (Cytokines) RN - 0 (Interleukin-1) RN - 0 (Interleukin-6) RN - 0 (Tumor Necrosis Factor-alpha) SB - IM MH - Actins/biosynthesis MH - Acute Disease MH - Animals MH - Cytokines/*biosynthesis MH - Female MH - Interleukin-1/biosynthesis MH - Interleukin-6/biosynthesis MH - Liver/metabolism MH - Lung/metabolism MH - Male MH - Mice MH - Mice, Inbred Strains MH - Pancreas/metabolism MH - Pancreatitis/*metabolism/physiopathology MH - Pancreatitis, Acute Necrotizing/metabolism/physiopathology MH - Spleen/metabolism MH - Tumor Necrosis Factor-alpha/biosynthesis EDAT- 1997/08/01 00:00 MHDA- 1997/08/01 00:01 CRDT- 1997/08/01 00:00 PHST- 1997/08/01 00:00 [pubmed] PHST- 1997/08/01 00:01 [medline] PHST- 1997/08/01 00:00 [entrez] AID - 10.1023/a:1018886120711 [doi] PST - ppublish SO - Dig Dis Sci. 1997 Aug;42(8):1783-8. doi: 10.1023/a:1018886120711.