Abstracts
2000 Digestive Disease Week

# 2302 Gabexate Mesilate Promotes Neutrophil Apoptosis and Attenuates Serum Cytokines Alterations in Human Acute Pancreatitis.
Han-Ming Chen, Miin-Fu Chen, Tsann-Long Hwang, Yi-Yin Jan, Ji- Chan Chen, Taipei, Taiwan

Introduction: Inappropriate acivation of neutrophils within tissues plays a crucial role in the development of organs dysfunction in acute pancreatitis. The delay of programmed cell death or apoptosis of neutrophils is associated with the failure in termination of neutrophil-mediated inflammatory response. We investigated the effects of gabexate mesilate on neutrophil apoptosis in the progress of severe acute pancreatitits. Methods: Patients with acute pancreatitis who met the following criteria: onset less than 48 hr and APACHE-II score>8 or/and Ranson score>3 were enrolled and randomly grouped in this study. All patients were admitted to the intensive care unit. Gabexate mesilate was delivered through a central vein catheterization at the dose of 1mg/kg/hr afteradmission (Group B, n=15). Group A received vehecle infusion only (n= 11). Neutrophils and plasma were isolated from whole venous blood at 3 time points: at admision, 12 hr post-treatment and 48 hr post-treatment of acute pancreatitis. Neutrophil apoptosis was quantified by immunofluorescence flow cytometry of 3' terminal deoxynucleotidyl transferase nick end labeling and PI staining. Cytokine detection was through special commercialized kits, which were based on enzyme-linked immunosorbent assay. Results: Neutrophil apoptosis was significantly inhibited with an event evident 12 hr and 48 hr aftertreatment of acute pancreatitis. Gabexate mesilate infusion significantly promoted neutrophil apoptosis. Levels of inflammatory mediators (TNF-aand IL-6) which levels increased 12 hr and 48 hr after treatment of acute pancreatitis was notably attenuated by gabexate mesilate. Levels of other inflammatory mediators (IL1-band IL-8) which levels increased 12 hr after treatment of acute pancreatitis was unaltered. Whereas level of IL-10, which was increased 48 hr after treatment of acute pancreatitis, was only slightly decreased. Conclusions: Gabexate mesilate given early in the course of acute pancreatitis lessens the magnitudes of changes of inflammatory mediators and the inhibition of neutrophil apoptosis. It has little effect on the anti-inflammatory cytokine IL-10, however.