Single doses of FK506 and OKT3 reduce severity in early experimental acute pancreatitis.
OBJECTIVE
To find out if two immunomodulatory drugs used in organ transplantation (FK506 (tacrolimus) and OKT3 (Orthoclone) would reduce early inflammatory complications in experimental acute pancreatitis.


METHODS
Laboratory study.


METHODS
University hospital, Germany.


METHODS
36 Balb/c mice.


METHODS
Pancreatitis induced by 7 intraperitoneal injections of cerulein 50 microg/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.


METHODS
Serum amylase activity and interleukin-6 (IL-6) concentrations; histological damage to pancreas and lungs, apoptotic cells in pancreas; and myeloperoxidase activity in lungs.


RESULTS
No animal died during the experiment. At 12h serum amylase activity and IL-6 concentrations were increased in all 3 groups, but highest in the OKT3 group. The pancreatic histological score, apoptosis, and inflammatory infiltration were lower in the two experimental groups than controls, but the degree of vacuolisation of acinar cells was similar. Packed cell volume was higher in the control than the experimental groups, and pulmonary damage and myeloperoxidase activity were less in the experimental groups than the controls.


CONCLUSIONS
Single therapeutic doses of FK506 and OKT3 reduced the early severity of pancreatitis, pulmonary damage, and haemoconcentration in mice. Single doses of FK506 or OKT3 may therefore be effective in preventing the early complications of pancreatitis.
Mayer
J M
JM
Department of General Surgery, University of Ulm, Germany.
Laine
V J
VJ
Gezgin
A
A
Kolodziej
S
S
Nevalainen
T J
TJ
Storck
M
M
Beger
H G
HG
D000208:Acute Disease; D000681:Amylases / Q000097:blood; D000818:Animals; D017209:Apoptosis; D002108:Ceruletide; D005260:Female; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D015850:Interleukin-6 / Q000097:blood; D008168:Lung / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D016853:Muromonab-CD3 / Q000008:administration & dosage / Q000494:pharmacology*; D010179:Pancreas / Q000473:pathology; D010195:Pancreatitis / Q000139:chemically induced / Q000188:drug therapy*; D009195:Peroxidase / Q000378:metabolism; D016559:Tacrolimus / Q000008:administration & dosage / Q000494:pharmacology*
D007166:Immunosuppressive Agents; D015850:Interleukin-6; D016853:Muromonab-CD3; D002108:Ceruletide; D009195:Peroxidase; D000681:Amylases; D016559:Tacrolimus