Objective—To evaluate whether immunosuppressive
doses of cyclosporine (CsA) have an adverse effect on
the liver, kidney, and pancreatic beta cells of pigs.
Animals—8 juvenile 8-week-old Landrace X Large
White crossbred pigs.
Procedure—CsA (100 to 140 mg/kg) was administered
orally to euglycemic pigs to reach whole blood
trough concentrations of approximately 1500 ng/mL.
To determine pancreatic beta cell function, plasma Cpeptide
and insulin concentrations were measured in
response to IV administration of glucose, glucagon,
arginine, and oral administration of glucose. Effects
on liver and kidney were determined by monitoring
serum measurements of liver function and serum creatinine
Results—Plasma concentrations of C-peptide were
significantly lower in euglycemic CsA-treated pigs,
compared with control pigs, following IV administration
of glucose, glucagon, arginine, and oral administration
of glucose. Furthermore, the glucose clearance rate
was decreased in euglycemic CsA-treated pigs, compared
with control pigs. Serum creatinine concentrations
and 4 of 7 serum measurements of liver function
were not adversely affected by CsA administration.
Serum concentrations of bilirubin and albumin were
significantly increased, and serum alanine aminotransferase
activity was significantly decreased in CsA-treated
pigs, compared with control pigs. Histologic evaluation
of liver and kidney sections revealed no pathologic
findings in CsA-treated or control pigs.
Conclusions and Clinical Relevance—In our study,
immunosuppressive doses of CsA caused an impairment
of porcine pancreatic beta cell function, but did
not have toxic effects on the kidney. However, on the
basis of changes in serum bilirubin and albumin concentrations
and alanine aminotransferase activity,
subclinical toxic effects on the liver did occur when
immunosuppressive doses of CsA were administered.
(Am J Vet Res 2002;63:1501–1506)