Importance of cytokines, nitric oxide, and apoptosis in the pathological process of necrotizing pancreatitis in rats

László Leindler, E. Morschl, F. László, Y. Mándi, T. Takács, Katalin Jármai, Gyula Farkas

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

Objectives: Ischemia-reperfusion injury can be involved in the pathophysiology of acute necrotizing pancreatitis. The aim of our study was to determine the production of cytokines, tumor necrosis factor (TNF) and interleukin-6 (IL-6), the activation of the inducible nitric oxide synthase (iNOS), and the development of apoptosis during this pathologic process. Methods: Acute pancreatitis was produced in male Wistar rats by injection of 200 μL of 6% taurocholic acid into the main pancreatic duct in combination with the temporary (15 minutes) occlusion of the inferior splenic artery. Six and 24 hours later, the histologic damage was evaluated, and serum amylase, TNF, IL-6 levels, and INOS and apoptotic activity from pancreatic and pulmonary tissues were determined. Results: Twenty-four hours after the induction of pancreatitis, the mortality rate was 63%. During this period, the serum TNF and IL-6 levels were permanently high (50 ± 12 and 58 ± 10 U/Ml and 7083 ± 1610 and 6790 ± 850 U/Ml after 6 and 24 hours, respectively). The INOS activity showed an increasing tendency in the pancreas, and a decrease following an initial increase in the lung (from 4.2 ± 0.6 to 5 ± 0.4 and from 6.8 ± 0.6 to 3.8 ± 0.5 pmol/min/mg protein after 6 and 24 hours, respectively). Histologic examination confirmed severe necrotizing pancreatitis. In the pancreas, the apoptotic activity increased significantly (from 4 ± 4 to 27 ± 5/mm2 at 6 and 24 hours), while in the lungs, following an initial increase it declined during the course of necrotizing pancreatitis (from 49 ± 4 to 11 ± 6/mm2 at 6 and 24 hours). Conclusion: Our results indicate that intraductal taurocholic acid and ischemia-reperfusion provokes severe acute necrotizing pancreatitis with a high mortality rate and leads to systemic inflammatory reaction, which appears to be the consequence of the activation of the cytokine cascade and iNOS. The degree of NO overproduction by iNOS corresponds with the apoptotic process in the pancreas and the lung.

Original languageEnglish
Pages (from-to)157-161
Number of pages5
JournalPancreas.
Volume29
Issue number2
DOIs
Publication statusPublished - Aug 2004

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Pathologic Processes
Pancreatitis
Nitric Oxide
Nitric Oxide Synthase Type II
Acute Necrotizing Pancreatitis
Apoptosis
Cytokines
Pancreas
Interleukin-6
Lung
Taurocholic Acid
Tumor Necrosis Factor-alpha
Splenic Artery
Mortality
Pancreatic Ducts
Amylases
Reperfusion Injury
Serum
Reperfusion
Wistar Rats

Keywords

  • Acute pancreatitis
  • Apoptosis
  • Cytokine
  • Nitric oxide
  • Systemic inflammatory reaction (SIRS)

ASJC Scopus subject areas

  • Gastroenterology
  • Endocrinology

Cite this

Importance of cytokines, nitric oxide, and apoptosis in the pathological process of necrotizing pancreatitis in rats. / Leindler, László; Morschl, E.; László, F.; Mándi, Y.; Takács, T.; Jármai, Katalin; Farkas, Gyula.

In: Pancreas., Vol. 29, No. 2, 08.2004, p. 157-161.

Research output: Contribution to journalArticle

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abstract = "Objectives: Ischemia-reperfusion injury can be involved in the pathophysiology of acute necrotizing pancreatitis. The aim of our study was to determine the production of cytokines, tumor necrosis factor (TNF) and interleukin-6 (IL-6), the activation of the inducible nitric oxide synthase (iNOS), and the development of apoptosis during this pathologic process. Methods: Acute pancreatitis was produced in male Wistar rats by injection of 200 μL of 6{\%} taurocholic acid into the main pancreatic duct in combination with the temporary (15 minutes) occlusion of the inferior splenic artery. Six and 24 hours later, the histologic damage was evaluated, and serum amylase, TNF, IL-6 levels, and INOS and apoptotic activity from pancreatic and pulmonary tissues were determined. Results: Twenty-four hours after the induction of pancreatitis, the mortality rate was 63{\%}. During this period, the serum TNF and IL-6 levels were permanently high (50 ± 12 and 58 ± 10 U/Ml and 7083 ± 1610 and 6790 ± 850 U/Ml after 6 and 24 hours, respectively). The INOS activity showed an increasing tendency in the pancreas, and a decrease following an initial increase in the lung (from 4.2 ± 0.6 to 5 ± 0.4 and from 6.8 ± 0.6 to 3.8 ± 0.5 pmol/min/mg protein after 6 and 24 hours, respectively). Histologic examination confirmed severe necrotizing pancreatitis. In the pancreas, the apoptotic activity increased significantly (from 4 ± 4 to 27 ± 5/mm2 at 6 and 24 hours), while in the lungs, following an initial increase it declined during the course of necrotizing pancreatitis (from 49 ± 4 to 11 ± 6/mm2 at 6 and 24 hours). Conclusion: Our results indicate that intraductal taurocholic acid and ischemia-reperfusion provokes severe acute necrotizing pancreatitis with a high mortality rate and leads to systemic inflammatory reaction, which appears to be the consequence of the activation of the cytokine cascade and iNOS. The degree of NO overproduction by iNOS corresponds with the apoptotic process in the pancreas and the lung.",
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T1 - Importance of cytokines, nitric oxide, and apoptosis in the pathological process of necrotizing pancreatitis in rats

AU - Leindler, László

AU - Morschl, E.

AU - László, F.

AU - Mándi, Y.

AU - Takács, T.

AU - Jármai, Katalin

AU - Farkas, Gyula

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N2 - Objectives: Ischemia-reperfusion injury can be involved in the pathophysiology of acute necrotizing pancreatitis. The aim of our study was to determine the production of cytokines, tumor necrosis factor (TNF) and interleukin-6 (IL-6), the activation of the inducible nitric oxide synthase (iNOS), and the development of apoptosis during this pathologic process. Methods: Acute pancreatitis was produced in male Wistar rats by injection of 200 μL of 6% taurocholic acid into the main pancreatic duct in combination with the temporary (15 minutes) occlusion of the inferior splenic artery. Six and 24 hours later, the histologic damage was evaluated, and serum amylase, TNF, IL-6 levels, and INOS and apoptotic activity from pancreatic and pulmonary tissues were determined. Results: Twenty-four hours after the induction of pancreatitis, the mortality rate was 63%. During this period, the serum TNF and IL-6 levels were permanently high (50 ± 12 and 58 ± 10 U/Ml and 7083 ± 1610 and 6790 ± 850 U/Ml after 6 and 24 hours, respectively). The INOS activity showed an increasing tendency in the pancreas, and a decrease following an initial increase in the lung (from 4.2 ± 0.6 to 5 ± 0.4 and from 6.8 ± 0.6 to 3.8 ± 0.5 pmol/min/mg protein after 6 and 24 hours, respectively). Histologic examination confirmed severe necrotizing pancreatitis. In the pancreas, the apoptotic activity increased significantly (from 4 ± 4 to 27 ± 5/mm2 at 6 and 24 hours), while in the lungs, following an initial increase it declined during the course of necrotizing pancreatitis (from 49 ± 4 to 11 ± 6/mm2 at 6 and 24 hours). Conclusion: Our results indicate that intraductal taurocholic acid and ischemia-reperfusion provokes severe acute necrotizing pancreatitis with a high mortality rate and leads to systemic inflammatory reaction, which appears to be the consequence of the activation of the cytokine cascade and iNOS. The degree of NO overproduction by iNOS corresponds with the apoptotic process in the pancreas and the lung.

AB - Objectives: Ischemia-reperfusion injury can be involved in the pathophysiology of acute necrotizing pancreatitis. The aim of our study was to determine the production of cytokines, tumor necrosis factor (TNF) and interleukin-6 (IL-6), the activation of the inducible nitric oxide synthase (iNOS), and the development of apoptosis during this pathologic process. Methods: Acute pancreatitis was produced in male Wistar rats by injection of 200 μL of 6% taurocholic acid into the main pancreatic duct in combination with the temporary (15 minutes) occlusion of the inferior splenic artery. Six and 24 hours later, the histologic damage was evaluated, and serum amylase, TNF, IL-6 levels, and INOS and apoptotic activity from pancreatic and pulmonary tissues were determined. Results: Twenty-four hours after the induction of pancreatitis, the mortality rate was 63%. During this period, the serum TNF and IL-6 levels were permanently high (50 ± 12 and 58 ± 10 U/Ml and 7083 ± 1610 and 6790 ± 850 U/Ml after 6 and 24 hours, respectively). The INOS activity showed an increasing tendency in the pancreas, and a decrease following an initial increase in the lung (from 4.2 ± 0.6 to 5 ± 0.4 and from 6.8 ± 0.6 to 3.8 ± 0.5 pmol/min/mg protein after 6 and 24 hours, respectively). Histologic examination confirmed severe necrotizing pancreatitis. In the pancreas, the apoptotic activity increased significantly (from 4 ± 4 to 27 ± 5/mm2 at 6 and 24 hours), while in the lungs, following an initial increase it declined during the course of necrotizing pancreatitis (from 49 ± 4 to 11 ± 6/mm2 at 6 and 24 hours). Conclusion: Our results indicate that intraductal taurocholic acid and ischemia-reperfusion provokes severe acute necrotizing pancreatitis with a high mortality rate and leads to systemic inflammatory reaction, which appears to be the consequence of the activation of the cytokine cascade and iNOS. The degree of NO overproduction by iNOS corresponds with the apoptotic process in the pancreas and the lung.

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