Single doses of FK506 and OKT3 reduce severity in early experimental acutepancreatitis

Objective: To find out if two immunomodulatory drugs used in organ transpla ntation (FK506 (tacrolimus) and OKT3 (Orthoclone) would reduce early inflam matory complications in experimental acute pancreatitis. Design: Laboratory study. Setting: University hospital, Germany. Animals: 36 Balb/c mice. Interventions: Pancreatitis induced by 7 intraperitoneal injections of ceru lein 50 mu g/kg at hourly intervals followed by FK506 0.32 mg/kg, OKT3 0.6 mg/kg, or 0.9% sodium chloride (controls) (n = 12 in each group). 12 hours after induction of pancreatitis the animals were killed. Main outcome measures: Serum amylase activity and interleukin-6 (IL-6) conc entrations; histological damage to pancreas and lungs, apoptotic cells in p ancreas; and myeloperoxidase activity in lungs. Results: No animal died during the experiment. At 12h serum amylase activit y and IL-6 concentrations were increased in all 3 groups, but highest in th e OKT3 group. The pancreatic histological score, apoptosis, and inflammator y infiltration were lower in the two experimental groups than controls, but the degree of vacuolisation of acinar cells was similar. Packed cell volum e was higher in the control than the experimental groups, and pulmonary dam age and myeloperoxidase activity were less in the experimental groups than the controls. Conclusion: Single therapeutic doses of FK506 and OKT3 reduced the early se verity of pancreatitis, pulmonary damage, and haemoconcentration in mice. S ingle doses of FK506 or OKT3 may therefore be effective in preventing the e arly complications of pancreatitis.