Acute-phase response of the rat pancreas protects against further aggression with severe necrotizing pancreatitis.
OBJECTIVE
To test the hypothesis that the specific acute-phase response program of the pancreas is a powerful emergency defense mechanism that is beneficial during acute pancreatitis.


METHODS
Prospective, randomized, controlled animal study.


METHODS
Research laboratory in a university medical school.


METHODS
Female Wistar rats, weighing 250 to 300 g.


METHODS
An acute-phase response was induced in rats subjected to hyperstimulation with cerulein. The development of the acute-phase reaction was monitored by the expression of the pancreatitis-associated protein I. In control animals, no acute-phase response was induced. After the first experimental procedure at periods of 2, 48, or 168 hrs, the pancreas was challenged by inducing severe necrotizing pancreatitis with retrograde infusion of taurocholate into the pancreatic duct. The course of necrohemorrhagic pancreatitis and survival of the rats to the challenge was monitored with time.


RESULTS
Forty-eight hours after the onset of edematous pancreatitis, the acute-phase response was strong, as judged by the overexpression of mRNA, which encoded the pancreatitis-associated protein I, and the resulting increase in concentrations of this protein in the pancreas. When necrotizing pancreatitis was induced, the survival rate was significantly higher than in the corresponding control group. In contrast, expression of the pancreatitis-associated protein I was not detectable after 2 hrs, indicating that the acute phase had not fully developed, nor after 168 hrs when the acute phase had ended. In both cases, challenge by necrotizing pancreatitis led to similar survival rates in cerulein-treated and control rats.


CONCLUSIONS
The acute-phase response of the pancreas seems to be a powerful emergency defense mechanism against further pancreatic aggression, as shown by the improved survival of the animals. The factors mediating this protection are unknown. Due to the strong overexpression of the pancreatitis-associated protein I during the climax of the acute phase, this protein might be involved in the defense mechanism.
Fiedler
F
F
Department of Anesthesiology and Intensive Care, Klinikum Mannheim, Fakultät für Klinische Medizin der Universität Heidelberg, Germany.
Croissant
N
N
Rehbein
C
C
Iovanna
J L
JL
Dagorn
J C
JC
van Ackern
K
K
Keim
V
V
D000208:Acute Disease; D000209:Acute-Phase Proteins / Q000378:metabolism*; D000210:Acute-Phase Reaction / Q000209:etiology / Q000378:metabolism*; D000818:Animals; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D002108:Ceruletide; D004195:Disease Models, Animal; D005260:Female; D005765:Gastrointestinal Agents; D037181:Lectins, C-Type; D010179:Pancreas / Q000378:metabolism*; D010195:Pancreatitis / Q000378:metabolism; D019283:Pancreatitis, Acute Necrotizing / Q000378:metabolism* / Q000473:pathology; D000073718:Pancreatitis-Associated Proteins; D051381:Rats; D017208:Rats, Wistar
D000209:Acute-Phase Proteins; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D005765:Gastrointestinal Agents; D037181:Lectins, C-Type; D000073718:Pancreatitis-Associated Proteins; C000612141:REG3A protein, human; C000612144:Reg3b protein, rat; D002108:Ceruletide