Linked Life Data

9393251

Source:http://linkedlifedata.com/resource/pubmed/id/9393251

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
1997-12-16
pubmed:abstractText
The morbidity and mortality associated with acute pancreatitis are primarily a result of pancreatic parenchymal necrosis and the development of marked pulmonary dysfunction. Recent evidence suggests that both of these conditions are propagated by interleukin (IL)-1 beta and tumor necrosis factor (TNF)-alpha, which are produced in large quantities within these organs. Because the generation of these cytokines occurs in a predictable manner early in the development of acute pancreatitis, we aimed to determine whether cytokine gene processing could be inhibited in vivo and what effects this would have on pancreatitis severity. Mild [caerulein, 50 micrograms/kg/hour intraperitoneally (IP) x 4; n = 40] or severe (choline-deficient diet; n = 40) necrotizing pancreatitis was induced in NIH swiss mice. Animals were randomly given a novel small molecule (CNI-1493; 10 mg/kg IP) known to inhibit macrophage production of TNF and IL-1 in vitro by inhibiting translation of TNF mRNA into protein. Control animals received IP vehicle. All animals with acute pancreatitis showed dramatic up-regulation of the IL-1 beta and TNF-alpha genes. Those animals receiving CNI-1493 demonstrated attenuated production of both species of mRNA in pancreatic as well as pulmonary tissue (P < 0.01). Markers of pancreatitis severity such as serum amylase and lipase, as well as pancreatic necrosis, were decreased in animals treated with CNI-1493 (all P < 0.05). Posttranscriptional blockade of TNF production precludes induction of the proinflammatory cytokine cascade that normally occurs during acute pancreatitis. This lack of cytokine gene processing in the pancreas and lungs results in dramatic reductions in tissue damage and pancreatitis severity, which is not model dependent. This is the first time that a small molecule has been shown to influence this disease.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0003-1348
pubmed:author
pubmed:issnType
Print
pubmed:volume
63
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1045-9; discussion 1049-50
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:9393251-Amylases, pubmed-meshheading:9393251-Animals, pubmed-meshheading:9393251-Caerulein, pubmed-meshheading:9393251-Choline Deficiency, pubmed-meshheading:9393251-DNA Primers, pubmed-meshheading:9393251-Disease Models, Animal, pubmed-meshheading:9393251-Female, pubmed-meshheading:9393251-Gastrointestinal Agents, pubmed-meshheading:9393251-Gene Expression Regulation, pubmed-meshheading:9393251-Hydrazones, pubmed-meshheading:9393251-Interleukin-1, pubmed-meshheading:9393251-Lipase, pubmed-meshheading:9393251-Male, pubmed-meshheading:9393251-Mice, pubmed-meshheading:9393251-Pancreatitis, Acute Necrotizing, pubmed-meshheading:9393251-Polymerase Chain Reaction, pubmed-meshheading:9393251-RNA, Messenger, pubmed-meshheading:9393251-Severity of Illness Index, pubmed-meshheading:9393251-Tumor Necrosis Factor-alpha, pubmed-meshheading:9393251-Up-Regulation
pubmed:year
1997
pubmed:articleTitle
Small molecule inhibition of tumor necrosis factor gene processing during acute pancreatitis prevents cytokine cascade progression and attenuates pancreatitis severity.
pubmed:affiliation
Department of Surgery, University of South Florida, Tampa 33612, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S.