Effects of cyclosporine and tacrolimus (FK 506) on acute pancreatitis in mice
Y. Echigo, K. Inoue, M. Kogire, R. Doi, S. Higashide, S. Sumi, H. Kaji and M. Imamura
First Department of Surgery, Kyoto University, Japan.
OBJECTIVE: To use mice to examine the effects of cyclosporine and
tacrolimus (FK 506) on two forms of acute pancreatitis often seen after
clinical organ transplantation. METHODS AND DESIGN: In the first
experiment, male CD-1 mice received cyclosporine (10 mg/kg), tacrolimus
(0.32 mg/kg), or saline solution (control) subcutaneously once a day for 10
days. On the 11th day, acute edematous pancreatitis was induced by
ceruletide (cerulein). In the second experiment, female ICR mice were fed
with a choline-deficient, ethionine-supplemented (CDE) diet for 72 hours to
induce necrotizing pancreatitis. After 30 hours on the CDE diet, the mice
received cyclosporine (10 mg/kg), tacrolimus (0.32 mg/kg), or saline
solution (control) subcutaneously twice daily for 3 days. RESULTS: The
pancreatic dry-to-wet weight ratios after ceruletide injections
significantly decreased in mice treated with cyclosporine but did not with
tacrolimus. Cyclosporine also significantly increased serum amylase levels,
but tacrolimus did not. Cyclosporine or tacrolimus alone did not produce
pancreatitis. In the CDE diet groups there was a significant difference in
survival among the cyclosporine-treated, the tacrolimus-treated, and the
control groups. CONCLUSIONS: Cyclosporine or tacrolimus given alone does
not induce acute pancreatitis. In contrast, cyclosporine can adversely
affect the course of acute edematous pancreatitis, and both
immunosuppressants may worsen the survival of mice with acute hemorrhagic
necrotizing pancreatitis. This study also demonstrated that the
deteriorating effect of tacrolimus is less potent than that of
cyclosporine.
