The Effect of Local and Systemic Administration of Soluble IL-15 Receptor -Chain in Experimental Corneal Transplantation

Abstract

Abstract: : Purpose: To investigate and compare the effects of local and systemic administration of sIL-15 receptor α-chain (sIL-15Rα) in a mouse model of corneal transplantation. Method: In a model of murine allografting [C57BL10 mice (H2b) to BALB/c mice (H2d)] we treated recipients of the grafts as follows: (1) topical treatment with sIL-15Rα (3x per day for 20 days); (2) systemic treatment i.p. using 3 different schedules: (a) sIL-15Rα or control non-sense M4 protein or PBS from day 0-20 post-graft at a dose of 60γg/day/animal; (b) sIL-15Rα or M4 protein from day 0 –10 post-graft; and (c) sIL-15Rα or M4 protein from day 5-15 after corneal grafting. Immunohistochemistry of donor corneas after local treatment and CBA from the DLN was performed at 3, 6 and 9d post-graft. Results: Systemic treatment with sIL-15Rα using both the 0-20 and 0-10 days post-graft protocol significantly prolonged corneal graft survival. Control administration of non-sense M4 protein had no effect on prolongation of corneal graft survival compared to untreated (PBS) controls. In contrast, administration of sIL-15Rα using the 5-15 days post graft protocol led to an accelerated tempo of corneal graft rejection. Local treatment with sIL-15Rα significantly prolonged graft survival in comparison with non-treated or M4 protein treated graft recipients. Immunohistochemistry showed reduced F4/80⁺, CD11b⁺, MoMa-2⁺ and mannose receptor positive macrophage infiltration of corneal grafts topically treated with sIL-15Rα. No statistically significant difference was found in production of IFN-γ, TNF-α and IL-6 by cells from DLN between groups treated with sIL-15Rα and M4 protein. However, the production of IL-12p70, IL-10 and MCP-1 was significantly higher in the group treated with sIL-15Rα than treated with M4 protein. Conclusions: These results indicate that IL-15-IL-15R blockade is effective in delaying corneal graft rejection when used both systematically and topically. In both cases, the effect was observed only when blockage was in place from the time of grafting.

Keywords: cornea: basic science • transplantation • immunomodulation/immunoregulation