Leflunomide therapy following penetrating keratoplasty in the rat.
BACKGROUND
The isoxal derivative, leflunomide (LF), is a new potent immunosuppressive which has been shown to be effective in preventing autoimmune disorders and reactions leading to organ transplantation rejection. LF is thought to antagonise cytokine activity and thereby to interfere with T-helper-cell-dependent B- and T-lymphocyte proliferation.


METHODS
We used LF to treat corneal allograft rejection in the rat, comparing its effect with that of cyclosporin A (CSA). Corneal buttons were grafted from Lewis/Brown Norway rats to Lewis recipients. Animals were randomly assigned to the following treatment groups: I, untreated; II, CSA (10 mg/kg i.m.); III, LF (2.5 mg/kg p.o.); IV, LF (5 mg/kg p.o.); V, LF (10 mg/kg p.o.); VI, combined therapy (LF 10 mg/kg p.o. and CSA 10 mg/kg i.m). Treatment began on the first postoperative day and was continued until rejection occurred.


RESULTS
The mean graft rejection time in the untreated allogeneic group was 12 days. A significant delay in graft rejection was observed in all treatment groups compared with group I (P < 0.001). Further, the delay in graft rejection resulting from combined therapy (group VI) was statistically significant compared with all other groups (P < 0.001).


CONCLUSIONS
These results suggest that (a) LF when used alone is as effective as CSA in treating corneal allograft rejection in the rat, and (b) when LF and CSA are combined they are more effective than either drug alone in the prolongation of allograft survival.
Coupland
S E
SE
Augenabteilung, Klinikum Steglitz, Berlin, Germany.
Klebe
S
S
Karow
A C
AC
Krause
L
L
Kruse
H
H
Bartlett
R R
RR
Hoffmann
F
F
D000284:Administration, Oral; D000818:Animals; D003315:Cornea / Q000187:drug effects / Q000473:pathology; D016572:Cyclosporine / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007555:Isoxazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D015948:Keratoplasty, Penetrating; D000077339:Leflunomide; D011897:Random Allocation; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D014184:Transplantation, Homologous
D007166:Immunosuppressive Agents; D007555:Isoxazoles; D016572:Cyclosporine; D000077339:Leflunomide