Technetium-99m-labeled white blood cells: a new method to define the local and systemic role of leukocytes in acute experimental pancreatitis.
OBJECTIVE
We developed a new method to quantitate leukocyte accumulation in tissues and used it to examine the time course and severity of acute experimental pancreatitis.


BACKGROUND
Leukocyte activation and infiltration are believed to be critical steps in the progression from mild to severe pancreatitis and responsible for many of its systemic complications.


METHODS
Pancreatitis of graded severity was induced in Sprague-Dawley rats with a combination of caerulein and controlled intraductal infusion. Technetium-99m (99mTc)-labeled leukocytes were quantified in pancreas, lung, liver, spleen, and kidney and compared with myeloperoxidase activity. The severity of pancreatitis was ascertained by wet/dry weight ratio, plasma amylase, and trypsinogen activation peptide in the pancreas. The time course of leukocyte accumulation was determined over 24 hours.


RESULTS
Pancreatic leukocyte infiltration correlated well with tissue myeloperoxidase concentrations. In mild pancreatitis, leukocytes accumulated only in the pancreas. Moderate and severe pancreatitis were characterized by much greater leukocyte infiltration in the pancreas than in mild disease (p < 0.01), and increased 99mTc radioactivity was detectable in the lung as early as 3 hours. 99mTc radioactivity correlated directly with the three levels of pancreatitis.


CONCLUSIONS
Mild pancreatitis is characterized by low-level leukocyte activation and accumulation in the pancreas without recruitment of other organs; marked leukocyte accumulation was found in the pancreas and in the lung in more severe grades of pancreatitis. These findings provide a basis for the pathophysiologic production of cytokines and oxygen free radicals, which potentiate organ injury in severe pancreatitis. This study validates a new tool to study local and systemic effects of leukocytes in pancreatitis as well as new therapeutic hypotheses.
Werner
J
J
Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston 02114, USA.
Dragotakes
S C
SC
Fernandez-del Castillo
C
C
Rivera
J A
JA
Ou
J
J
Rattner
D W
DW
Fischman
A J
AJ
Warshaw
A L
AL
D000208:Acute Disease; D000818:Animals; D002108:Ceruletide; D004195:Disease Models, Animal; D018450:Disease Progression; D005765:Gastrointestinal Agents; D007962:Leukocytes / Q000276:immunology*; D008297:Male; D010195:Pancreatitis / Q000097:blood / Q000139:chemically induced / Q000175:diagnosis* / Q000276:immunology*; D019275:Radiopharmaceuticals; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012720:Severity of Illness Index; D019690:Technetium Tc 99m Exametazime
D005765:Gastrointestinal Agents; D019275:Radiopharmaceuticals; D019690:Technetium Tc 99m Exametazime; D002108:Ceruletide