Open AccessSynergism of the malononitrilamides 279 and 715 with cyclosporine A in the induction of long‐term cardiac allograft survival
Author(s) -
Lindner J. K.,
Zanil N.
Publication year - 1998
Publication title -
transplant international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.998
H-Index - 82
eISSN - 1432-2277
pISSN - 0934-0874
DOI - 10.1111/j.1432-2277.1998.tb01140.x
Subject(s) - leflunomide , medicine , urology , metabolite , pharmacology , rheumatoid arthritis
We tested here the effects of malononitrilamide (MNA) 279 and MNA 715 (derivatives of A771726, the active metabolite of leflunomide) in monotherapy and in combination with cyclosporine A (CSA) on heterotopically transplanted rat cardiac allografts (BN) [Brown Norway Lewis]. Both MNAs (5–20 mg/kg) displayed a dose‐dependent increase of efficacy. The combination of CSA (5 mg/kg) with the MNAs (5 and 10 mg/kg) showed a synergistic effect in the prolongation of allograft survival and in the induction of long‐term allograft survival. To investigate the immunological mechanism responsible for long‐term allograft survival, we transplanted second set (BN) and third party (Dark Agouti) skin allografts on the tail of long‐term surviving rats. The cause for long‐term allograft survival turned out to be a donor‐specific tolerance. We formulate a hypothesis for the mechanism of the synergism of the combination MNA + CSA in the induction of tolerance.