Ameliorative Effect of Adalimumab on Experimentally Induced Acute Pancreatitis in Rats

Abstract

In this study, the effects of adalimumab (ADA), a fully humanized IgG1 monoclonal antibody to tumor necrosis factor α, on experimentally acute pancreatitis (AP) were examined. Healthy Wistar rats (n = 32) were randomly divided into 4 groups: group 1, AP; group 2, AP + ADA; group 3, control (physiologic saline), and group 4, physiologic saline + ADA (n = 8/group). Acute pancreatitis was induced with a retrograde injection of 3% sodium (Na)-taurocholate into the common biliopancreatic duct. Adalimumab was simultaneously administered at 50 mg/kg intraperitoneally for groups 2 and 4. Physiologic saline was administered instead of Na-taurocholate for non-AP groups. After 24 hours, serum amylase, lactate dehydrogenase, pancreatic myeloperoxidase, and malondialdehyde activities, along with pancreatic histopathology, were examined. Adalimumab treatment significantly decreased serum amylase activity (AP, 2778.25 ± 298.80; AP + ADA, 2143.13 ± 221.69; control, 1541.00 ± 148.39; ADA, 1143.00 ± 256.30 U/L; P < 0.001), lactate dehydrogenase activity (AP, 2978.37 ± 364.65; AP + ADA, 2582.75 ± 164.23; control 931.25 ± 135.93; ADA, 582.62 ± 99.37 U/L; P < 0.001), myeloperoxidase activity (AP, 1.44 ± 0.20; AP + ADA, 0.86 ± 0.01; control, 0.60 ± 0.17; ADA, 0.41 ± 0.00 U/g of wet tissue; P < 0.001), malondialdehyde activity (AP, 16.94 ± 3.98; AP + ADA, 7.66 ± 2.27; control, 9.07 ± 1.00; ADA, 3.58 ± 0.30 nmol/g; P < 0.01), and total histopathologic scores (AP, 2.75 ± 0.16; AP + ADA, 1.50 ± 0.19; control, 0.00 ± 0.00; ADA, 0.00 ± 0.00; P < 0.001). These results support the idea that adalimumab might be beneficial for severity of AP.