Beneficial effects of hydrocortisone in a model of experimental acute pancreatitis

Background: Proinflammatory cytokines like TNF-alpha and IL-8 have been thought to play a pivotal role in the propagation of severe acute pancreatitis (AP) and the development of its systemic complications, particularly acute lung injury. Objective: To investigate the effects of pretreatment with hydrocortisone on the production of cytokines and the occurrence of acute lung injury in rabbits with AP, Methods: AP was induced in 17 rabbits by infusion of 5% chenodeoxycholic acid into the pancreatic duct, followed by ductal ligation. The rabbits were allocated to pretreatment with subcutaneous and intravenous hydrocortisone (25 mg/kg, respectively; n = 7) or 0.9% saline (n = 10) 30 min before induction of AP. Rabbits were observed for 12 h. Serum amylase, lipase, TNF-alpha, IL-8, glucose, calcium and leukocyte count were measured every 3 h. At the end of the experimental period, ascitic fluid was collected and tissue specimens from the pancreas, lungs and kidney were obtained. Results: Hydrocortisone pretreatment improved survival from 40 to 100%. Serum TNF-alpha and IL-8 were lower in the hydrocortisone group than in the control group at 6 h (p = 0.006 and p < 0.001, respectively). Hydrocortisone abolished leukopenia (p < 0.001), hyperamylasemia (p = 0.05), the occurrence of acute lung injury and reduced the volume of ascites. Conclusions: Our findings suggest a role for TNF-alpha and IL-8 in mediating the progress of AP from a local disease into a systemic illness, Hydrocortisone should be tested experimentally after the induction of AP and clinically as a prophylactic measure to avoid severe AP induced by endoscopic retrograde cholangiopancreaticography.