Leflunomide: is a new oral agent in treatment of acute pancreatitis?

Objectives: Nuclear factor-kappaB (NF-kappaB) is a potent mediator in several steps of acute pancreatitis. Leflunomide is a novel immunomodulating drug that is also a potent inhibitor of NF-kappaB activation. The aim of this study was to investigate the effects of leflunomide pretreatment in severe necrotizing pancreatitis in rats.

Methods: Fifty rats were randomly divided into 5 groups. Severe necrotizing pancreatitis was induced by retrograde injection of 3% sodium taurocholate into the common biliopancreatic duct. Leflunomide (10 mg/kg) was given intragastrically for 2 doses before the experiment. Serum amylase activity, pancreatic histopathologic condition, malondialdehyde level, myeloperoxidase enzyme activity, nitric oxide level, and pulmonary changes were assessed.

Results: Leflunomide pretreatment significantly ameliorated pancreatic hemorrhage, edema, and neutrophil infiltration and decreased histopathological score compared with the untreated severe necrotizing pancreatitis group (pathological score [mean +/- SEM]: 6.70 +/- 1.19 vs 12.36 +/- 1.08 in the leflunomide treated and untreated groups, respectively, P < 0.01). Pulmonary changes was decreased in the leflunomide treated group (3.90 +/- 0.45 vs 4.75 +/- 0.25, respectively). Change in pulmonary alveolar distention was significant. Although serum amylase levels also decreased, the difference was not significant (5922 +/- 3290 vs 15547 +/- 5090 U/mL).

Conclusions: Leflunomide is a beneficial agent in the severe form of acute pancreatitis in rats and should be considered as a potential agent for treatment of acute pancreatitis.