Effects of spironolactone on corneal allograft survival in the rat.
OBJECTIVE
Spironolactone has recently been shown to have suppressive effects on several immunoactive and proinflammatory cytokines. In this study, we investigated the effects of spironolactone on the prevention of corneal allograft rejection in a MHC class I/II mismatch rat corneal transplant model.


METHODS
Grafted animals for corneal survival analysis were assigned to receive either spironolactone suspension (orally, 100 mg/kg/day, n = 7), phosphate-buffered saline (PBS, orally, same volume as spironolactone, n = 9) or remained untreated (n = 16). Additional grafted rats treated with spironolactone (n = 6) or PBS (n = 8) were sacrificed on day 12 for quantitative RT-PCR analysis for mechanistic studies.


RESULTS
Mean (+/-SEM) graft survival was significantly prolonged in animals receiving spironolactone (14.9 +/- 2.0 days) compared with both PBS-treated (12.3 +/- 1.2 days, p = 0.007) and untreated controls (13.0 +/- 1.0 days, p = 0.01). We found a decrease in corneal neovascularization in spironolactone-treated rats compared with the PBS-treated group, although the difference was not statistically significant. Spironolactone affected both systemic (down-regulation of CD25+ cells in spleen) and local immune response (up-regulation of IL-10 in cornea).


CONCLUSIONS
We present initial results demonstrating anti-inflammatory effects of spironolactone.
Department of Ophthalmology, Charité - University Medicine Berlin, Berlin, Germany. ljilja69@yahoo.com
Ljiljana
L
Otasevic
Nianqiao
N
Gong
Thomas
T
Ritter
Stefan
S
Mergler
Uwe
U
Pleyer
D000284:Administration, Oral; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000917:Antibody Formation / Q000187:drug effects; D003315:Cornea / Q000098:blood supply / Q000378:metabolism; D016039:Corneal Transplantation / Q000009:adverse effects; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects*; D006648:Histocompatibility; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D016753:Interleukin-10 / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000209:etiology / Q000517:prevention & control; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D013148:Spironolactone / Q000008:administration & dosage / Q000494:pharmacology*; D013154:Spleen / Q000378:metabolism; D013997:Time Factors; D014181:Transplantation Immunology; D014184:Transplantation, Homologous
D000893:Anti-Inflammatory Agents; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D053645:Interleukin-2 Receptor alpha Subunit; D016753:Interleukin-10; D013148:Spironolactone