Therapeutic effectiveness of adalimumab in experimental acute pancreatitis

Acute pancreatitis is a local inflammatory disease of pancreas. Tumor necrosis factor alpha (TNF-alpha) has a central role in the pathogenesis and its related systemic complications. The aim of this study is to evaluate the therapeutic effectiveness of TNF inhibitor adalimumab in severe necrotizing pancreatitis (SNP) model in rats.METHODSSeventy female Wistar albino rats weighing median 250 grams randomly divided into seven groups. Rats were divided into the following groups; group 1: SHAM laparatomy, group 2: SNP, group 3: SNP and saline intraperitoneally (IP), group 4: Adalimumab(ADA) 2mg/kg IP and SNP, group 5: ADA 4mg/kg and SNP, group 6: ADA 2mg/kg and group 7: ADA 4mg/kg. SNP was induced by complete pancreatic duct obstruction and cerulein hyperstimulation (50 microgram/kg intraperitoneally). Animals were killed at 24 hours. Pancreata were prepared for hematoxylin and eosin staining. Serum pancreatic amylase activity, pancreatic edema, inflammation, necrosis, fat necrosis, bleeding were assessed.RESULTSAdalimumab treatment was not found to decrease serum pancreatic amylase levels statistically significant(SNP, 13160±3208,9; SNP+ADA 2mg/kg, 13946±1393,1; SNP+ADA 4mg/kg, 12298±2133,8 U/L; p>0,5). Adalimumab treatment significantly decreased total histopathologic scores (SNP, 18,5±1,2; SNP+ADA 2mg/kg, 12,3 ±1,2; SNP+ADA 4mg/kg, 8,3±5,5; p<0,005). Adalimumab, itself, was not found to induce acute pancreatitis (pancreatic amylase levels for; control, 1833,2±233,6; ADA 4mg/kg 1337,5±204,3; ADA 2mg/kg 1498±82,2; p=1).CONCLUSIONAdalimumab 4 mg/kg treatment was found to decrease edema, inflammation, necrosis, fat necrosis, bleeding and total pancreas pathologic scores statistically significantly. We did not observe statistically significant reduction in pancreatic amylase levels which was we suppose because of our severe pancreatits model. This study might be a basis for new experimental trials investigating the potential therapeutic role of adalimumab.?