Specific therapy for local and systemic complications of acute pancreatitis with monoclonal antibodies against ICAM-1

Objective To analyze the lime points and levels of the expression of adhesi on molecules in the pancreas and lung in pancreatitis of different severiti es, and to assess whether treatment with a monoclonal antibody against inte rcellular adhesion molecule-1 (ICAM-1) can reduce local and systemic compli cations, Background The outcome of severe acute pancreatitis relates to its pulmonar y and septic complications. Leukocyte adhesion and infiltration, both media ted by ICAM-1, are central events in the pathogenesis of necrotizing pancre atitis. Methods Expression of ICAM-1 at different time points was assessed by immun ohistochemistry and Western blot analysis in pancreas and lungs from rats w ith mild edematous or severe necrotizing pancreatitis. ICAM-1 expression wa s correlated with leukocyte infiltration and histologic changes. The possib le therapeutic effect of monoclonal antibodies against ICAM-1 was assessed by measuring pancreatic and lung injury, Results In edematous pancreatitis, increased ICAM-1 expression in pancreas was evident by 8 hours but did not occur in lung. In contrast, ICAM-1 was u pregulated at 3 hours in the pancreas and at 12 hours in lung in necrotizin g pancreatitis. Increased expression of ICAM-1 preceded leukocyte infiltrat ion. Treatment of severe necrotizing pancreatitis with monoclonal antibodie s against ICAM-1 decreased both local pancreatic injury and systemic lung i njury compared with untreated controls, Conclusions Upregulation of ICAM-1 and subsequent leukocyte infiltration ap pear to be significant mediators of pancreatic and pulmonary injury in panc reatitis, and both the onset and extent correlate with severity, The time c ourse should permit effective prevention of tissue damage by treatment with ICAM-1 antibodies.