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Imunodeppression induced by thalidomide and cyclosporine in heterotopic heart transplantation of rabbits

BACKGROUND: Because of its anti-inflammatory and immunodepressive effects, thalidomide has been used for the treatment of dermatologic diseases and of host-versus-graft disease in patients submitted to bone marrow transplantation. In the present study we evaluated the immunodepressive action of thalidomide alone or in combination with cyclosporine on the prevention of rejection of a heterotopic cardiac allograft in rabbits. METHODS: Fifty rabbits were used, 25 of them as donors and 25 as recipients. Recipient animals were divided into five groups (n = 5 each): Group I (control) _ non-immunodepressed animals, Group II (immunodepressed animals with cyclosporine at the dose of 10 mg/kg/day), Group III ( immunodepressed animals with thalidomide at the dose of 100 mg/kg/day), Group IV ( immunodepressed animals with cyclosporine at the dose of 5.0 mg/kg/day ), and Group V ( immunodepressed animals with cyclosporine at the dose of 5.0 mg/kg/day in combination with thalidomide at the dose of 50 mg/kg/day). Medications were administered through an orogastric catheter starting on the day before the transplant. The heart of the donors was implanted in the abdomen of the recipients. RESULTS: The combination of thalidomide and cyclosporine showed the lowest histopathological rejection score (p < 0.05). Thalidomide administered alone or in combination with cyclosporine was effective against rejection, significantly increasing the survival (p < 0.01) of animals submitted to heterotopic heart transplantation in the abdominal position. CONCLUSIONS: The effectiveness of the combination of thalidomide and cyclosporine may represent an important application in the field of pharmacological imunosuppression in organ transplants.

Thalidomide; Cyclosporine; Heart transplantation; Rabbits


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