Synergism of RAD and cyclosporin A in prevention of acute rat corneal allograft rejection.
OBJECTIVE
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.
Reis
Alexander
A
Eye Clinic, Heinrich-Heine University, Duesseldorf, Germany. reis@uni-duesseldorf.de
Megahed
Mosaad
M
Reinhard
Thomas
T
Godehardt
Erhard
E
Braunstein
Christian
C
Sundmacher
Rainer
R
D000208:Acute Disease; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D016572:Cyclosporine / Q000627:therapeutic use*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D000068338:Everolimus; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015948:Keratoplasty, Penetrating; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D020123:Sirolimus / Q000031:analogs & derivatives / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000276:immunology; D014184:Transplantation, Homologous
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D000068338:Everolimus; D020123:Sirolimus