TC-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 accumulati on in tissues and used it to examine the time course and severity of a cute experimental pancreatitis. Background Leukocyte activation and in filtration are believed to be critical steps in the progression from m ild to severe pancreatitis and responsible for many of its systemic co mplications. Methods Pancreatitis of graded severity was induced in Sp rague-Dawley rats with a combination of caerulein and controlled intra ductal infusion. Technetium-99m (Tc-99m)-labeled leukocytes were quant ified in pancreas, lung, liver, spleen, and kidney and compared with m yeloperoxidase activity. The severity of pancreatitis was ascertained by wet/dry weight ratio, plasma amylase, and trypsinogen activation pe ptide in the pancreas. The time course of leukocyte accumulation was d etermined over 24 hours. Results Pancreatic leukocyte infiltration cor related well with tissue myeloperoxidase concentrations. in mild pancr eatitis, leukocytes accumulated only in the pancreas. Moderate and sev ere pancreatitis were characterized by much greater leukocyte infiltra tion in the pancreas than in mild disease (p < 0.01), and increased Tc -99m radioactivity was detectable in the lung as early as 3 hours. Tc- 99m radioactivity correlated directly with the three levels of pancrea titis. Conclusions Mild pancreatitis is characterized by low-level leu kocyte activation and accumulation in the pancreas without recruitment of other organs; marked leukocyte accumulation was found in :he pancr eas and in the lung in more severe grades of pancreatitis. These findi ngs provide a basis for the pathophysiologic production of cytokines a nd oxygen free radicals, which potentiate organ injury in severe pancr eatitis. This study validates a new tool to study local and systemic e ffects of leukocytes in pancreatitis as well as new therapeutic hypoth eses.