Favorable efficacy of adalimumab treatment in experimental acute pancreatitis model

Abstract

Background: Acute pancreatitis is a clinical picture with a wide range of symptoms from mild inflammation to multiorgan failure and death. The aim of this study is to investigate the effects of Adalimumab (ADA) on inflammation and apoptosis in a cerulein-induced acute pancreatitis model in rats.

Methods: Experimental cerulein-induced acute pancreatitis model was created by applying 4 intraperitoneal cerulein injections at 1-h intervals. A total of 40 rats, 8 in each group, were randomly distributed into five groups. In the groups that ADA treatment was given, two different doses of ADA were administered 5 mg/kg and 20 mg/kg as low and high doses, respectively. The rats were sacrificed 12 h after the last intraperitoneal administration of ADA. Blood samples were obtained from each rat for amylase, IL-6, and IL-1β measurements. Hematoxylin and Eosin (H&E) stains were used to undertake the histopathological analysis of the pancreas. The terminal deoxynucleotidyl transferase-mediated nick-end-labeling (TUNEL) method was used to evaluate apoptosis.

Results: : Plasma amylase, IL-6, and IL-1β levels were significantly elevated in acute pancreatitis groups (p < 0.05). It was determined that both low (5 mg/kg) and high doses (20 mg/kg) of ADA ameliorated the parameters (plasma amylase, IL-6, and IL-1β) (p < 0.05). Although significant improvements were detected in the Schoenberg scoring system and the apoptotic index from the TUNEL method after highdose ADA treatment, no significant amelioration was observed in the histopathological examinations in the low-dose ADA group.

Discussion: : It has been determined that the administration of high-dose ADA effectively alleviated the symptoms of acute pancreatitis and reduced the level of apoptosis. In line with the findings of our study, we have predicted that high-dose (20 mg/kg) ADA can be used as an effective and safe drug in the treatment of patients with acute pancreatitis.

Keywords: Acute pancreatitis; Adalimumab; apoptosis; inflammation.

Figure 1

Hematoxylin and eosin staining of pancreatic tissue samples. A. Control group with normal pancreatic tissue, 20× magnification. B. Acute pancreatitis group, intralobular polymorphonuclear cell infiltration, vacuolation, necrosis and edema are seen, 20x magnification. C. Sp treated placebo group, vacuolization, edema, and inflammation are still existing, 20× magnification. D. Adalimumab treatment group, reduced polymorphonuclear cells, vacuolation, and edema with low dose, 20× magnification. E. Adalimumab treatment group with high dose, 20× magnification. (Polymorphonuclear cell infiltration, vacuolation, necrosis, and edema are marked with black arrows)

Figure 2

TUNEL technique shows the apoptotic status of study groups. A. Control group. No apoptotic cell is seen. B. Acute pancreatitis group. Increased apoptotic cells are seen. Apoptotic index is 4.7%. C. Sp treated placebo group, similar features with acute pancreatitis group. Apoptotic index is 5.3%. D. Adalimumab treatment group. Decreased apoptotic cells are seen with a low dose. Apoptotic index is 3.55% E. Adalimumab treatment group. Apoptotic index is 2.08% (TUNEL staining, ×20 magnification. Apoptotic cells are marked with black arrows).