Combined FTY720/cyclosporine treatment promotes graft survival and lowers the peripheral lymphocyte count in a murine cardiac allotransplantation model.
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.
Nikolova
Z
Z
Novartis Pharma Research, Novartis Pharma AG, CH-4002 Basel, Switzerland.
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Baumlin
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D000818:Animals; D016572:Cyclosporine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005260:Female; D000068876:Fingolimod Hydrochloride; D006085:Graft Survival / Q000187:drug effects*; D016027:Heart Transplantation; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D018655:Lymphocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D011409:Propylene Glycols / Q000494:pharmacology*; D013110:Sphingosine / Q000031:analogs & derivatives; D016042:Transplantation, Heterotopic; D014184:Transplantation, Homologous
D004338:Drug Combinations; D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D016572:Cyclosporine; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine