Synergism of RAD and cyclosporin A in prevention of acute rat corneal allograft rejection

Cornea. 2002 Jan;21(1):81-4. doi: 10.1097/00003226-200201000-00017.

Abstract

Purpose: The novel immunosuppressant RAD, 40-0-(2-hydroxy-ethyl)-rapamycin, has synergistic effects with cyclosporin A. The aim of this study was to evaluate the combined effect of RAD and cyclosporin A in the prevention of acute allograft rejection after murine corneal transplantation.

Methods: Fisher donor corneas were implanted into Lewis recipients. Postoperative evaluation included slit-lamp biomicroscopy and immunohistology. Treatment groups were comprised of rats treated orally with RAD 2.5 mg/kg/day, cyclosporin A 10 mg/kg/day, RAD 1.5 mg/kg/day plus cyclosporin A 5 mg/kg/day.

Results: Therapy with RAD 2.5 mg/kg and cyclosporin A 10 mg/kg led to a statistically significant and comparable prolongation of transplant survival. However. combination therapy was significantly superior. There was a significant reduction in the number of infiltrating cells in the animals treated with RAD and cyclosporin A.

Conclusions: This is the first study on the efficacy of a double drug regimen with RAD and cyclosporin A for the control of acute corneal allograft rejection. Combination therapy resulted in superior graft survival.

MeSH terms

  • Acute Disease
  • Animals
  • B-Lymphocytes / immunology
  • Cyclosporine / therapeutic use*
  • Drug Synergism
  • Drug Therapy, Combination
  • Everolimus
  • Graft Rejection / immunology
  • Graft Rejection / prevention & control*
  • Graft Survival / drug effects
  • Immunosuppressive Agents / therapeutic use*
  • Keratoplasty, Penetrating*
  • Rats
  • Rats, Inbred F344
  • Rats, Inbred Lew
  • Sirolimus / analogs & derivatives
  • Sirolimus / therapeutic use*
  • T-Lymphocytes / immunology
  • Transplantation, Homologous

Substances

  • Immunosuppressive Agents
  • Cyclosporine
  • Everolimus
  • Sirolimus