A comparative investigation of FK506 and cyclosporin A in murine corneal transplantation.
BACKGROUND
Acute rejection is the cause of over 50% of transplant opacifications in some immunological high-risk groups. More potent immunomodulating substances must be found in order to allow extended or individualised therapeutic options for combating rejection.


METHODS
Rats of the inbred strains Brown Norway and Lewis were used as donors and recipients, respectively. FK506 (Prograf) was administered intraperitoneally for 14 days in a dosage of 0.3 mg/kg bw, and cyclosporin A (CSA; Sandimmun) was administered, likewise for 14 days, in an intramuscular dosage of 10 mg/kg bw. The transplants were examined every 3rd day by slit-lamp microscopy. Every transplant was subjected to histological or immunohistological evaluation.


RESULTS
The average transplant survival period in the allogeneic strain combination was 7.9 days (SEM = 1.1). Therapy with FK506 led to a statistically significant prolongation of transplant survival to 17.1 days (SEM = 1.5, P < 0.05). Therapy with CSA delayed transplant rejection to 21 days (SEM = 0.0, P < 0.05). No statistically significant difference was found between the two therapeutic regimens. There were no significant histomorphologic differences in rejected grafts in the FK506- and CSA-treated animals.


CONCLUSIONS
In this study we have shown that FK506 is able to delay corneal allograft rejection at a much lower dosage than CSA without a higher incidence of side effects related to toxicity or overimmunosuppression.
Reis
A
A
Department of Pathology, Heinrich Heine University, Düsseldorf, Germany.
Reinhard
T
T
Sundmacher
R
R
Braunstein
S
S
Godehardt
E
E
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology; D003315:Cornea / Q000378:metabolism / Q000473:pathology; D016039:Corneal Transplantation; D016572:Cyclosporine / Q000627:therapeutic use*; D006084:Graft Rejection / Q000517:prevention & control; D006085:Graft Survival; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D011184:Postoperative Period; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D016559:Tacrolimus / Q000627:therapeutic use*; D013997:Time Factors; D014185:Transplantation, Isogeneic
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D016559:Tacrolimus