The effect of corticosteroid and cyclosporin A on murine corneal allograft rejection.
BACKGROUND
The immunomodulatory T-helper type 1 (Th1) cytokine interferon-gamma (IFN-gamma) was measured in serum and cornea to ascertain its general contribution to corneal graft rejection and to establish a rational basis for the decision for or against systemic therapy.


METHODS
Eight groups of differently treated BALB/c (H-2d) mice received a C3H (H-2 k) corneal graft. There was one saline-treated control group and two groups that received intramuscular cyclosporin A (CsA) for 14 or 40. Three groups received systemic or topical, systemic plus topical corticosteroid treatment, which was combined with CsA in two further groups. To measure the IFN-gamma level by enzyme-linked immunosorbent assay (ELISA), blood was taken by heart puncture and corneae were excised at the limbus.


RESULTS
Five days of systemic corticosteroid and 14 days of CsA had no significant effect on graft survival. A 40-day CsA treatment and a 40-day combined corticosteroid treatment significantly prolonged graft survival. An 80-day topical corticosteroid treatment produced additional prolongation. IFN-gamma could not be detected (limit of detection 25 pg/ml) in any of the serum samples, while significantly increased amounts of IFN-gamma were detected in the supernatants of the corneal tissue 13 or 14 days after allogeneic but not syngeneic corneal graft, corresponding to 9.5 pg, 5.1 pg and 1.8 pg per cornea.


CONCLUSIONS
The detection of Th1 cytokines in the cornea but not the serum of mice at the time of allograft rejection is in accordance with the finding of long-lasting dose-dependent immunosuppression of topical steroids and the inefficacy of short-term systemic CsA and corticosteroids.
Zhang
E P
EP
Freie Universität Berlin, Universitätsklinikum Benjamin Franklin, Augenklinik und Poliklinik, Germany.
Schulte
F
F
Bulfone-Paus
S
S
Hoffmann
F
F
D000818:Animals; D003315:Cornea / Q000378:metabolism; D016039:Corneal Transplantation / Q000276:immunology; D016572:Cyclosporine / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D009883:Ophthalmic Solutions; D011239:Prednisolone / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D014184:Transplantation, Homologous
D007166:Immunosuppressive Agents; D009883:Ophthalmic Solutions; D007371:Interferon-gamma; D016572:Cyclosporine; D011239:Prednisolone; C021322:prednisolone hemisuccinate