Effect of topical interleukin-1 receptor antagonist (IL-1ra) on corneal allograft survival in presensitized hosts

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Abstract
Topical interleukin-1 receptor antagonist (IL-1ra) promotes corneal allograft survival in naive hosts by suppressing local antigen-presenting cell function and allosensitization. The purpose of these experiments was to test whether IL-1ra could likewise promote transplant survival in pre-sensitized hosts. Orthotopic corneal grafts were performed into immunized (N = 65) and naive (N = 40) BALB/c recipients from fully disparate (C57BL/6) or minor H-only disparate (B10.D2) mice. Allograft recipients were randomized to receive treatment with IL-1ra or vehicle only. Immunization to both MHC and minor H alloantigens was associated with accelerated graft rejection. IL-1ra treatment had no significant impact on overall graft longevity or the early incidence of graft rejection in pre-immunized recipients of fully-disparate corneal allografts (P = 0.25). Similarly, although rejection of corneal grafts in hosts immunized to minor H alloantigens occurred more slowly in mice treated with IL-1ra than in controls (P = 0.04), overall graft survival at 8 weeks was comparable (P = 0.07) among the two groups. The accelerated rejection of corneal allografts in presensitized hosts is not materially affected by IL-1ra, particularly if the host has been immunized to donor MHC alloantigens. These data confirm that the role of IL-1ra in corneal transplantation is primarily limited to downmodulating the afferent, not expression, arm of alloimmunity.