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Interleukin 1 Receptor Antagonist Suppresses Allosensitization in Corneal Transplantation

1998; American Medical Association; Volume: 116; Issue: 10 Linguagem: Inglês

10.1001/archopht.116.10.1351

1538-3601

Jun Yamada,

Ocular Surface and Contact Lens

Objective: To delineate the mechanisms by which topical interleukin 1 receptor antagonist (IL-1RA) treatment promotes orthotopic corneal allograft survival.Methods: Corneal buttons were prepared from eyes of C57BL/6 mice and placed orthotopically in normal or neovascularized (high-risk) eyes of BALB/c mouse recipients.Topical IL-1RA (or vehicle alone) was applied to grafts 3 times daily until the grafted eyes were enucleated.Corneal specimens were evaluated for content of Langerhans cells.A week after enucleation, 1 group of recipients was tested for allospecific delayed-type hypersensitivity elicited by intrapinnae injections of donor splenocytes.In companion experiments, a second group of mice that underwent transplantation, IL-1RA treatment, and enucleation was challenged with orthotopic skin grafts from B10.D2 donor mice (sharing minor H antigens with C57BL/6 mice) to determine whether the second group of mice could reject grafts bearing corneal donor minor H alloantigens in an accelerated fashion.Results: Mice whose orthotopic corneal allografts were treated topically with IL-1RA acquired neither donor-specific delayed-type hypersensitivity (PϽ.001) nor the capacity to reject orthotopic donor-type skin allografts in an accelerated manner (PϽ.05), whereas controls treated with vehicle alone developed delayed-type hypersensitivity and rejected B10.D2 grafts in an accelerated manner.Moreover, IL-1RA-treated grafts placed in both high-risk (P = .01)and normal-risk (P = .004)eyes displayed significantly reduced levels of infiltrating Langerhans cells compared with vehicle-treated controls.Conclusions: Topical IL-1RA promotes corneal allograft survival in large part by preventing activity of recipient Langerhans cells, and thereby preventing these cells from inducing systemic allosensitization.These data suggest that IL-1 plays a key role in promoting allosensitization when corneal allografts are placed orthotopically.Clinical Relevance: Suppression of allosensitization by topical IL-1RA may prove a clinically useful method for enhancing corneal transplant survival.