Combined FTY720/cyclosporine treatment promotes graft survival and lowers the peripheral lymphocyte count in a murine cardiac allotransplantation model

Z Nikolova, A Hof, Y Baumlin, RP Hof - Transplantation, 2001 - journals.lww.com
Z Nikolova, A Hof, Y Baumlin, RP Hof
Transplantation, 2001•journals.lww.com
Background. FTY720 lowers the peripheral lymphocyte count (PLC) by accelerating the
migration of circulating lymphocytes to secondary lymphoid organs. We investigated the
efficacy of combined FTY720+ cyclosporine (CsA) treatment versus monotherapy on
prolonging graft survival and on lowering the PLC. Methods. BALB/c hearts were
heterotopically grafted in C3H mice. FTY720 was administered alone or in combination with
CsA. PLC and body weight were determined on day 7, day 28, or the day of rejection …
Abstract
Background.
FTY720 lowers the peripheral lymphocyte count (PLC) by accelerating the migration of circulating lymphocytes to secondary lymphoid organs. We investigated the efficacy of combined FTY720+ cyclosporine (CsA) treatment versus monotherapy on prolonging graft survival and on lowering the PLC.
Methods.
BALB/c hearts were heterotopically grafted in C3H mice. FTY720 was administered alone or in combination with CsA. PLC and body weight were determined on day 7, day 28, or the day of rejection.
Results.
Combining FTY720 with CsA prolonged, dose-dependently and significantly, the allograft survival. FTY720, but not CsA, lowered the PLC dose-dependently. The granulocyte count was not reduced in any group. FTY720 concentrations were not influenced by the CsA co-administration.
Conclusions.
Combined FTY720 and CsA treatment was well tolerated, promoted graft survival, and suppressed the inflammatory allo-response. The PLC lowering correlated well with the antirejection effects in the two-drug regimens, suggesting that the PLC might guide FTY720 therapy at low doses.
Lippincott Williams & Wilkins
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