Influence of pancreatic enzyme content on experimental acute pancreatitis.
BACKGROUND
Some studies demonstrate the crucial role of proteases in the pathogenesis of acute pancreatitis (AP). Systemic release of proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) has been demonstrated in AP, yet the mechanism of activation remains unclear. Furthermore, it is not known if the amount of pancreatic enzyme in the pancreas determines the production of proinflammatory cytokines.


OBJECTIVE
To determine whether there is a link between the pancreatic enzyme content and the production of cytokines and consequently the systemic lesions observed in AP.


METHODS
Forty-seven animals were divided into three groups: group I had a high pancreatic enzyme level (with and without AP), group II had a low pancreatic enzyme level (cerulein infusion: 0.133 microg x kg(-1) x h(-1)) (with and without AP), and group III were the controls. AP was induced by injection of 5% sodium taurocholate into the pancreatic duct. To evaluate the pancreatic enzyme contents before AP, trypsinogen and amylase analysis was carried out on pancreatic tissue collected after the animals were killed. Two hours after induction of AP, concentrations of pancreatic enzymes and trypsinogen activation peptide (TAP) in serum, ascitic fluid, and pancreatic tissue were determined. The ascitic fluid was assayed for TNF-alpha and the serum was assayed for IL-6 with ELISA kits. Systemic lesions were sought on the basis of hepatic mitochondrial respiratory function measured polarographically.


CONCLUSIONS
The administration of physiological doses of cerulein diminishes the pancreatic enzyme and TAP levels, the production of proinflammatory cytokines, and the liver mitochondrial dysfunction observed in AP, suggesting that the pancreatic enzyme content is an important factor in the severity of AP.
Coelho
Ana Maria de Mendonça
AM
Department of Gastroenterology, Laboratory of Medical Investigation (LIM/35), University of São Paulo Medical School, São Paulo, Brazil.
Machado
Marcel Cerqueira Cesar
MC
Cunha
José Eduardo Monteiro
JE
Sampietre
Sandra Nassa
SN
Abdo
Emilio Elias
EE
D000208:Acute Disease; D000818:Animals; D015850:Interleukin-6 / Q000096:biosynthesis; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism; D009842:Oligopeptides / Q000032:analysis; D010084:Oxidation-Reduction; D010179:Pancreas / Q000201:enzymology*; D010195:Pancreatitis / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D015850:Interleukin-6; D009842:Oligopeptides; D014409:Tumor Necrosis Factor-alpha; C080396:trypsinogen activation peptide