Specific therapy for local and systemic complications of acute pancreatitis with monoclonal antibodies against ICAM-1.
OBJECTIVE
To analyze the time points and levels of the expression of adhesion molecules in the pancreas and lung in pancreatitis of different severities, and to assess whether treatment with a monoclonal antibody against intercellular adhesion molecule-1 (ICAM-1) can reduce local and systemic complications.


BACKGROUND
The outcome of severe acute pancreatitis relates to its pulmonary and septic complications. Leukocyte adhesion and infiltration, both mediated by ICAM-1, are central events in the pathogenesis of necrotizing pancreatitis.


METHODS
Expression of ICAM-1 at different time points was assessed by immunohistochemistry and Western blot analysis in pancreas and lungs from rats with mild edematous or severe necrotizing pancreatitis. ICAM-1 expression was correlated with leukocyte infiltration and histologic changes. The possible 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 6 hours but did not occur in lung. In contrast, ICAM-1 was upregulated at 3 hours in the pancreas and at 12 hours in lung in necrotizing pancreatitis. Increased expression of ICAM-1 preceded leukocyte infiltration. Treatment of severe necrotizing pancreatitis with monoclonal antibodies against ICAM-1 decreased both local pancreatic injury and systemic lung injury compared with untreated controls.


CONCLUSIONS
Upregulation of ICAM-1 and subsequent leukocyte infiltration appear to be significant mediators of pancreatic and pulmonary injury in pancreatitis, and both the onset and extent correlate with severity. The time course should permit effective prevention of tissue damage by treatment with ICAM-1 antibodies.
Werner
J
J
Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston 02114, USA.
Z'graggen
K
K
Fernández-del Castillo
C
C
Lewandrowski
K B
KB
Compton
C C
CC
Warshaw
A L
AL
D000208:Acute Disease; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis* / Q000276:immunology*; D008168:Lung / Q000378:metabolism; D008297:Male; D010179:Pancreas / Q000378:metabolism; D019283:Pancreatitis, Acute Necrotizing / Q000378:metabolism* / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D013997:Time Factors
D000911:Antibodies, Monoclonal; D018799:Intercellular Adhesion Molecule-1