Effect of Anti-TNFα Therapy by Infliximab against Pancreatic Tissue Damage in Severe Acute Necrotizing Pancreatitis

摘要

© 2021 Razi Vaccine and Serum Research Institute. All rights reserved.Nowadays, it is difficult to find a more complicated inflammatory disease of the abdominal organs in its pathogenesis than acute pancreatitis (AP). The application of antimediatory drugs and antimetabolites is the most promising direction in the correction of inflammatory pathological processes. The study of possible applications of a new group of drugs (monoclonal antibodies) that may trigger inflammation is also of great interest. The present study aimed to study the effect of infliximab on the lethality, volume, and nature of pancreatic lesions in severe necrotizing ductal pancreatic necrosis. The study was conducted on female Wistar rats (n=30) of similar age in the weight range of 200-250g. All manipulations were performed under general anesthesia by intraperitoneal injection of zoletil at a dose of 60 mg/kg, as well as chloral hydrate at a dose of 125 mg/kg. Model of severe acute necrotizing pancreatitis was performed through the injection of 0.5 ml of a buffer solution containing a bile acid salt-sodium taurocholate introductory. The animals were divided into the following groups: Group A (n=6): normal values; Group B (n=6): the mortality study was conducted in acute destructive pancreatitis in a period of 24 h; Group C (n=6): the simulation of acute severe necrotic pancreatitis was performed in this group along with the study of the volume of pancreatic lesions for a period of 6 h from the moment of modeling; Group D (n=6): in this group, the effect of infliximab (at a dose of 60 mkg/kg) was studied on mortality in severe destructive pancreatitis for a period of 24 h from the moment of modeling; Group E (n=6): in this group, the effect of infliximab (at a dose of 120 mkg/kg) was studied on the volume of pancreatic lesions in severe destructive pancreatitis for a period of 6 h from the moment of modeling. During the assessment of pancreatic damage, the mean±SD volume of pancreatic lesions was determined to be 34.8±1.2 in a period of 6 h after modeling. Assessment of pancreatic damage in group E and the protective effect of infliximab at a dose of 60 mg/kg showed that the total volume of the necrotic pancreatic lesion was determined to be 21.3±1.4 after a period of 6 h from the moment of AP modeling. In the course of this study, it was revealed that the application of infliximab at a dose of 60 mcg/kg led to a pronounced positive effect on the pancreatic lesion, manifested by up to 50 decrease in mortality for one day in group D. Infliximab had a definite protective effect in AP, decreasing the volume of the injury, as well as the mortality rate by half for 24 h. Therapy with anti-tumor necrosis factor with infliximab could significantly reduce the volume of pancreatic lesions in severe forms of pancreatic necrosis, which contributed to a pronounced decrease in mortality for 1 day from the moment of pathology reproduction.