Abstracts
1999 Digestive Disease Week

# 2152 ADHESION MOLECULES CORRELATE WITH LUNG INJURY DURING ACUTE PANCREATITIS (AP).
Andrew H Lundberg, Univ of Tenn, Memphis, Memphis, TN; D N Granger, LSU Med Ctr, Shreveport, LA; J Russell, Louisiana State Univ Med Ctr, Shreveport, LA; O Sabek, J Henry, L W Gaber, M Kotb, A O Gaber, Univ of Tenn, Memphis, Memphis, TN

Lung injury is a major cause of patient morbidity in AP. The purpose of this study was to examine the mechanism of pulmonary infiltration and lung injury in AP. Swiss Webster female mice weighing 18-20 grams were fed the choline deficient ethionine supplemented diet (CDE) for 144 hours to induce severe AP with low mortality. Serum samples were collected for measurement of biochemical markers of AP and for the detection of cytokines. Cell surface adhesion molecule expression was quantitated by a sensitive radiolabelled monoclonal antibody technique. Neutrophil sequestration was mesured by the myeloperoxidase asay (MPO). Organ injury was graded histologically. CDE fed mice developed significant hyperamylasemia and hypoglycemia by 48 hours (p<0.01) and cytokine levels increased significantly by 48 hours over baseline (p<0.02). Pancreatic injury was demonstrated initially at 24 hours and peaked at 96-120 hours. Lung injury temporally lagged behind pancreatic injury but worsened throughout the experiment and peaked at 144 hours. Expression of ICAM in pulmonary endothelia was significantly increased above baseline at 48 hours (64.07 ± 6.23 vs. 95.51 ± 5.17 mg mAb/gram tissue; p<0.015) respectively, and peaked at 120 hours (146.26 ± 16.29 mg mAb/gram tissue; p<0.0001). VCAM also demonstrated constitutive expression at 0 hours and was upregulated by 48 hours as well (1.14 ± 0.11 vs. 3.33 ± 0.49 mg mAb/gram tissue; p<0.0001), respectively. Leukocyte infiltration increased gradually with significant MPO activity over baseline at 72 hours (7.24 ± 2.83 vs. 18.07 ± 3.84 activity units/gram tissue; p<0.05), i.e. 24 hours following ICAM and VCAM upregulation. Leukocyte infiltration peaked at 144 hours (26.24 ± 10.49 activity units/ gram tissue p<0.0001) and correlated with the onset and progression of histological injury. The results suggest that the cytokine inflammatory response induced in AP promotes upregulation of cellular adhesion molecules that correlate temporally to neutrophil sequestration and subsequently cause organ injury. The cytokine-adhesion molecule axis may provide a potential target for delayed intervention that ameliorates lung injury and morbidity in AP.

Copyright 1996 - 1999, SSAT, Inc.