The role of leukocytes in the production of oxygen-derived free radicals in acute experimental pancreatitis.

Oxygen-derived free radicals mediate an important step in the initiation of experimental acute pancreatitis in the ex vivo perfused canine pancreas model. In other organ systems, circulating leukocytes may serve as one source of oxygen-derived free radical production. The current experiments were designed to evaluate the role of circulating leukocytes in the generation of injury in this model. Four experimental groups of animals were studied: group I consisted of controls (n = 6); group II had white blood cell (WBC) depletion (n = 4) in which the recirculating whole blood perfusate was depleted of 98% of its circulating leukocytes; group III had oleic acid infusion (FFA) alone (n = 9), which induced pancreatitis; group IV had WBC depletion and FFA (n = 6), in which oleic acid was infused after depletion of the circulating leukocytes in the perfusate. During the 4-hour perfusion period, the pancreatic preparations were monitored hourly for the development of edema, weight gain, and release of alpha-amylase into the perfusate. Animals in groups I and group II manifested no gross edema, gained minimal weight, and did not manifest hyperamylasemia. Leukocyte depletion alone had no effect. In group IV animals marked edema, significant weight gain, and hyperamylasemia developed to the same extent as in group III animals. These results demonstrate that circulating leukocytes are not essential to the development of pancreatitis in this model and suggest that another source of oxygen-derived free radicals mediates this injury.