Diagnosis and management of chronic graft-versus-host disease.
The goal in transplantation is to obtain immunosuppressant combinations that decrease the incidence of acute and chronic rejection but cause fewer side effects. FTY720 is a new immunomodulator that prevents experimental allograft rejection without inhibiting T-cell activation. It is currently under clinical investigation for multiple sclerosis. We investigated whether FTY720 in combination with sirolimus (SRL) could cause renal toxicity in C57BL/6 mice when administered for 21 days. Serum creatinine and 24-hour urinary creatinine concentrations were assessed by enzymatic colorimetric assays. Urinary protein concentration was measured by the Bradford protein assay. Whereas serum creatinine levels were increased in FTY720 + SRL-treated animals, there were no changes in urinary volume, urinary protein levels, serum urea concentration, creatinine clearance, and kidney structure. Our findings suggested that FTY720 monotherapy for multiple sclerosis and other diseases could play an important immunomodulatory role without causing the side effects frequently observed with other transplantation regimens.