Effects of leflunomide and cyclosporine on myocutaneous allograft survival in the rat.
The immunosuppressive effects of leflunomide and cyclosporine were evaluated in a rat neurovascularized myocutaneous allograft model. Inbred Brown-Norway and Lewis rats were served as donors and recipients, respectively. All recipients were observed for 60 days or until allograft rejection occurred. All isograft controls (Lewis to Lewis, n=6) survived uneventfully. All control allografts (n=6) were rejected within 6 days. Allograft recipients (n=6) administered leflunomide (10 mg/kg/24 hr) rejected their allografts in 28.50+/-6.12 days, and allograft recipients (n=6), administered cyclosporine (5 mg/kg/24 hr) rejected their allografts in 24.33+/-10.48 days. When allograft recipients were administered a combination of leflunomide and cyclosporine (10 mg/kg/24 hr and 5 mg/kg/24 hr, respectively), all allografts survived to 60 days with only partial rejection of the skin of one graft. The neuromuscular function of the allografts of the rats receiving combination therapy was comparable to that of the isografts. The combination of leflunomide and cyclosporine controlled myocutaneous allorejection despite a strong immunological challenge.
Yeh
L S
LS
Department of Surgical Science, School of Veterinary Medicine, University of California, Davis 95616, USA.
Gregory
C R
CR
Griffey
S M
SM
Lecouteur
R A
RA
Morris
R E
RE
D000818:Animals; D016572:Cyclosporine / Q000494:pharmacology* / Q000627:therapeutic use; D005071:Evoked Potentials; D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects*; D006614:Hindlimb; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007555:Isoxazoles / Q000494:pharmacology* / Q000627:therapeutic use; D000077339:Leflunomide; D018482:Muscle, Skeletal / Q000637:transplantation*; D009416:Nerve Regeneration / Q000187:drug effects; D009431:Neural Conduction / Q000187:drug effects; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology; D010525:Peripheral Nerves / Q000637:transplantation; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D016038:Skin Transplantation / Q000276:immunology*
D007166:Immunosuppressive Agents; D007555:Isoxazoles; D016572:Cyclosporine; D000077339:Leflunomide