Abstracts
1999 Digestive Disease Week

# 2154 NECROTIZING PANCREATITIS RESULTS IN LOCAL AND SYSTEMIC UPREGULATION OF TRANSFORMING GROWTH FACTOR b1 (TGFb1): EVIDENCE FOR A COMMON MECHANISM OF INJURY
K A Joseph, J Kalish, H Yee, NYU Sch of Medicine, New York, NY; Peter Shamamian, New York Univ Med Ctr, New York, NY

Transforming growth factor b1 belongs to a family of multifunctional regulators of cell growth and differentiation. TGFb1 is one of three isoforms of TGFb that exert diverse effects depending on the target cell. It has been shown that there is an increase in TGFb1 in the pancreas after induction of acute pancreatitis suggesting a role for TGFb1 in pancreatic repair. Acute pancreatitis results in local pancreatic destruction and remote organ injury. Pulmonary failure results in significant morbidity and mortality in patients following pancreatitis. We hypothesize that TFGb1 plays a role not only locally in necrotizing pancreatitis but also in distant lung injury, suggesting a common mechanism. Methods: Twelve male Sprague Dawley rats were randomized into two groups. Acute necrotizing pancreatitis (NP) was induced in one group by retrograde infusion of 5% sodium taurocholate (1.5 ml/kg) into the pancreatic duct. As a control, the second group received a midline laporotomy and no infusion. Animals were sacrificed 24 h later. Serum amylase levels were determined and the pancreatic and lung tissues were stained with hematoxylin and eosin as well as immunostained for TGFb1. Necrosis and TGFb1 scoring was performed by an independent blinded pathologist. Results: There was a 2.5-fold increase in serum amylase (IU/L) in the NP group compared with the control group (4496.67 ± 1692.87 vs. 1765.5 ± 302.57, p < .002), and a ten-fold increase in necrosis scores of the pancreas (scale 1-4) between the NP and control groups (1.67 ± .82 vs. .17 ± .41, p <.002). In addition, there was a greater than three-fold increase in the pancreas TGFb1 score (scale 1-4) based on immunohistochemistry in the NP group compared with the control group (3.83 ± .41 vs. 1.00 ± 0.00, p= .000). The lungs of the NP group had a two-fold increase in TGFb1 score (scale 1-4) compared with the control group (2.33 ± .745 vs. 1.16 ± .372, p<.02). Conclusions: TGFb1 upregulation occurs in the pancreas and in the lungs within 24 h after induction of nectrotizing pancreatitis. In addition, we also demonstrate an increase in TGFb1 in the lungs of the NP group compared with the control group. The early expression of TGFb1 in necrotizing pancreatitis suggests a role not only in repair but also in the acute inflammatory process following injury. The upregulation of TGFb1 in the lungs within 24 h also supports the hypothesis that lung injury following necrotizing pancreatitis is mediated by the same mechanism that results in pancreatic inflammation. Therapy which limits pancreatic injury may also prevent remote end organ injury.

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