Infliximab: a new therapeutic agent in acute pancreatitis?
OBJECTIVE
Tumor necrosis factor alpha (TNF-alpha) has a central role in the pathogenesis of acute pancreatitis and related systemic complications. The aim of this study is to investigate the therapeutic effectiveness of monoclonal TNF antibody (infliximab) in acute edematous and severe necrotizing pancreatitis models in rats.


METHODS
One hundred rats were randomly divided into 10 groups. Acute edematous pancreatitis (AEP) was induced by injection of cerulein 20 microg/kg 4 times subcutaneously at hourly intervals. Severe necrotizing pancreatitis (SNP) was induced by retrograde injection of 3% taurocholate into the common biliopancreatic duct. Infliximab 8 mg/kg was given via intravenous infusion. Serum amylase activity, pancreatic histopathology, myeloperoxidase enzyme activity (MPO), and pulmonary changes were assessed.


RESULTS
Infliximab treatment significantly decreased serum amylase activity (11939 +/- 1914 U/L versus 3458 +/- 915 U/L, P < 0.001) and histopathologic score (4.1 +/- 0.5 versus 1.5 +/- 0.3, P < 0.001) in AEP. It also suppressed neutrophil infiltration and MPO activity of the pancreatic tissue. In SNP, infliximab treatment was found to decrease pathologic score (9.4 +/- 1.2 versus 3.6 +/- 0.8, P < 0.001) and serum amylase activity (20442 +/- 2375 versus 8990 +/- 1730, P < 0.01). It ameliorated both parenchymal and fatty tissue necrosis of the pancreas. Infliximab also alleviated alveolar edema and acute respiratory distress syndrome like pulmonary complications, but the difference was not significant.


CONCLUSIONS
Chimeric TNF antibody, infliximab, should be evaluated for treatment of acute pancreatitis.
Oruc
Nevin
N
Ege University, Faculty of Medicine, Gastroenterology Department, Izmir, Turkey.
Ozutemiz
A Omer
AO
Yukselen
Vahit
V
Nart
Deniz
D
Celik
Handan Ak
HA
Yuce
Gul
G
Batur
Yucel
Y
D000208:Acute Disease; D000681:Amylases / Q000097:blood; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D002108:Ceruletide; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D000069285:Infliximab; D008297:Male; D009336:Necrosis; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010195:Pancreatitis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D019283:Pancreatitis, Acute Necrotizing / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D009195:Peroxidase / Q000378:metabolism; D011654:Pulmonary Edema / Q000473:pathology / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar; D012720:Severity of Illness Index; D013656:Taurocholic Acid; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; D013656:Taurocholic Acid; D002108:Ceruletide; D000069285:Infliximab; D009195:Peroxidase; D000681:Amylases