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 accelera ting the migration of circulating lymphocytes to secondary lymphoid organs. We investigated the efficacy of combined FTY720+cyclosporine (CsA) treatme nt 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 det ermined on day 7, day 28, or the day of rejection. Results. Combining FTY720 with CsA prolonged, dose-dependently and signific antly, the allograft survival. FTY720, but not CsA, lowered the PLC dose-de pendently. The granulocyte count was not reduced in any group. FTY720 conce ntrations 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 low ering correlated well with the antirejection effects in the two-drug regime ns, suggesting that the PLC might guide FTY720 therapy at low doses.