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Titolo:
SMALL-MOLECULE INHIBITION OF TUMOR-NECROSIS-FACTOR GENE PROCESSING DURING ACUTE-PANCREATITIS PREVENTS CYTOKINE CASCADE PROGRESSION AND ATTENUATES PANCREATITIS SEVERITY
Autore:
DENHAM W; FINK G; YANG J; ULRICH P; TRACEY K; NORMAN J;
Indirizzi:
UNIV S FLORIDA,DEPT SURG,13000 BRUCE B DOWNS BLVD TAMPA FL 33612 UNIV S FLORIDA,DEPT SURG TAMPA FL 33612 PICOWER INST MED RES MANHASSET NY 00000
Titolo Testata:
The American surgeon
fascicolo: 12, volume: 63, anno: 1997,
pagine: 1045 - 1049
SICI:
0003-1348(1997)63:12<1045:SIOTGP>2.0.ZU;2-8
Fonte:
ISI
Lingua:
ENG
Soggetto:
POLYMERASE CHAIN-REACTION; INTERLEUKIN-1; ALPHA; RAT; EXPRESSION; INDUCTION; RNA;
Tipo documento:
Article
Natura:
Periodico
Citazioni:
25
Recensione:
Indirizzi per estratti:
Citazione:
W. Denham et al., "SMALL-MOLECULE INHIBITION OF TUMOR-NECROSIS-FACTOR GENE PROCESSING DURING ACUTE-PANCREATITIS PREVENTS CYTOKINE CASCADE PROGRESSION AND ATTENUATES PANCREATITIS SEVERITY", The American surgeon, 63(12), 1997, pp. 1045-1049

Abstract

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 ill vivo and what effects this would have on pancreatitis severity. Mild [caerulein, 50 mu g/kg/hour intraperitoneally (IF) x 4; n = 40] or severe (choline-deficient diet; n = 40) necrotizing pancreatitiswas induced in NIH swiss mice. Animals were randomly given a novel small molecule (CNI-1493; 10 mg/kg IF) 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 attenuatedproduction of both species of mRNA in pancreatic as well as pulmonarytissue (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 ofcytokine 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 beenshown to influence this disease.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 01/10/20 alle ore 15:06:21