Abstract
This study was designed to evaluate the possible role of cytokines (IL-1 and TNF-α)
in the pathogenesis of pancreatic injuries induced by pancreatic ischemia-reperfusion
and to evaluate the protective effect of the cytokine suppressive agent, FR167653,
against pancreatic injuries. Pancreatic ischemia-reperfusion was induced in rats by
ligating the celiac and caudate mesenteric arteries by small metallic clips for 45
min, after this ischemia, the metal clips were removed. Four hours after removing
the metal clips, the animals were used for the experiments. In this model, mild hyperamylsemia
and significant increases in pancreatic water and trypsin content were observed. Significant
increases in serum IL-1 and TNF-α were also observed, as compared with the control
rats. Pancreatic subcellular redistribution of lysosomal enzyme cathepsin B from the
lysosomal fraction to the zymogen fraction was also observed. However, treatment with
FR167653 at a dose of 0.5 mg/kg.hr significantly prevented all these pancreatic injuries.
These results indicate that cytokines such as IL-1 and TNF-α might be involved in
the pathogenesis of pancreatic injuries induced by ischemia-reperfusion, and that
a cytokine suppressive agent might be of therapeutic value for the treatment of pancreatic
ischemia.
