Hepatic Kupffer Cell Blockade Reduces Mortality of Acute Hemorrhagic Pancreatitis in Mice

Inflammatory cytokines derived from the liver may cause distant organ failure and death in severe pancreatitis To minimize liver cytokine release, we studied the effects of Kupffer cell blockade on the mortality rate and seventy of inflammation in a model of that disease Thirty mice were divided into three groups Group 1 received gadolinium chloride (1 mg/100 g intravenously), which blocks Kupffer cell activity, and regular food Groups 2 and 3 were fed a choline-deficient, ethionine-supplemented diet and developed severe pancreatitis Group 2 (control) received intravenous saline solution, and group 3 received gadolinium chloride Animals were killed at 72 hours Serum levels of tumor necrosis factor-α and interleukin-1β, interleukin-6, and interleukin-10 were determined by enzyme-linked immunosorbent assay Lung neutrophil infiltration was assessed by myeloperoxidase assay Pancreatic inflammation was scored in a blinded manner In a separate experiment, mortality rates were determined in saline- and gadolinium-treated animals (n = 100) Gadolinium reduced the levels of all the cytokines and lung myeloperoxidase (P <0 05) Gadolinium also reduced the mortality rate (52% vs 86%, P <0001) However, the degree of pancreatic inflammation was unchanged by gadolinium treatment These data support the hypothesis that mortality in severe pancreatitis may in part be related to the secondary release of hepatic cytokines.