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 m severe pancreatms To minmize hver cytokme release, we studied the effects of Kupffer cell blockade on the mortality rate and severity of mflammatlon m a model of that disease Thirty nuce were dlvlded mto three groups Group 1 received gadohmum chloride (1 mg/l00 g mtravenously), which blocks Kupffer cell acuvlty, and regular food Groups 2 and 3 were fed a chohne-deficient, etionine-supplemented diet and developed severe pancreatitls Group 2 (control) received intravenous sahne solution, and group 3 recewed gadohmum chlonde Animals were lulled at 72 hours Serum levels of tumor necrosis factor-a and mterlenkm-1p, mterleukmd, and mterlenkm-10 were determined by enzyme-hnked lmmunosorbent assay Lung neutrophll mfiltration was assessed by myeloperoxldase assay Pancreatic mflammauon was scored m a blinded manner In a separate experiment, mortahty rates were determmed m saline- and gadohnmm-treated animals (n = 100) Gadohmium reduced the levels of all the cytokmes and lung myeloperoxldase (P <0 0.5) Gadolmium also reduced the mortality rate (52% vs 86%,P<0 001) However, the degree of pancreatic mflammaaon was unchanged by gadohnmm treatment These data support the hypothesis that mortality m severe pancreauus may m part be related to the secondary release of hepauc cytokmes.