The effect of corticosteroid and cyclosporin A on murine corneal allograftrejection

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 t wo groups that received intramuscular cyclosporin A (CsA) for 14 or 40. Thr ee groups received systemic or topical, systemic plus topical corticosteroi d 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: F ive days of systemic corticosteroid and 14 days of CsA had no significant e ffect on graft survival. A 40-day CsA treatment and a 40-day combined corti costeroid treatment significantly prolonged graft survival. An 80-day topic al corticosteroid treatment produced additional prolongation. IFN-gamma cou ld not be detected (limit of detection 25 pg/ml) in any of the serum sample s, while significantly increased amounts of IFN-gamma were detected in the supernatants of the corneal tissue 13 or 14 days after allogeneic but not s yngeneic corneal graft, corresponding to 9.5 pg, 5.1 pg and 1.8 pg per corn ea. Conclusion: 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 findin g of long-lasting dose-dependent immunosuppression of topical steroids and the inefficacy of shortterm systemic CsA and corticosteroids.