The effect of local and systemic administration of soluble IL-15 receptor alpha-chain in experimental corneal transplantation [Abstract]

Kuffova, L., Taylor, J. A,, Duncan, L., Liew, Foo Y., Wei, Xiao-Qing ORCID: https://orcid.org/0000-0002-6274-8503 and Forrester, J. V 2003. The effect of local and systemic administration of soluble IL-15 receptor alpha-chain in experimental corneal transplantation [Abstract]. Investigative Ophthalmology & Visual Science 44 , U620-U620.

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Abstract

Purpose: To investigate and compare the effects of local and systemic administration of sIL-15 receptor {alpha}-chain (sIL-15R{alpha}) 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-15R{alpha} (3x per day for 20 days); (2) systemic treatment i.p. using 3 different schedules: (a) sIL-15R{alpha} or control non-sense M4 protein or PBS from day 0-20 post-graft at a dose of 60{gamma}g/day/animal; (b) sIL-15R{alpha} or M4 protein from day 0 –10 post-graft; and (c) sIL-15R{alpha} 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-15R{alpha} 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-15R{alpha} using the 5-15 days post graft protocol led to an accelerated tempo of corneal graft rejection. Local treatment with sIL-15R{alpha} 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-15R{alpha}. No statistically significant difference was found in production of IFN-{gamma}, TNF-{alpha} and IL-6 by cells from DLN between groups treated with sIL-15R{alpha} and M4 protein. However, the production of IL-12p70, IL-10 and MCP-1 was significantly higher in the group treated with sIL-15R{alpha} 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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Dentistry
Subjects:	R Medicine > R Medicine (General)
Publisher:	The Association for Research in Vision and Ophthalmology, Inc.
Last Modified:	21 Oct 2022 09:14
URI:	https://orca.cardiff.ac.uk/id/eprint/35695

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