Interleukin 1 receptor antagonist suppresses allosensitization in corneal transplantation.
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 (P<.001) nor the capacity to reject orthotopic donor-type skin allografts in an accelerated manner (P<.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.


CONCLUSIONS
Suppression of allosensitization by topical IL-1RA may prove a clinically useful method for enhancing corneal transplant survival.
Yamada
J
J
Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, Mass 02114, USA.
Dana
M R
MR
Zhu
S N
SN
Alard
P
P
Streilein
J W
JW
D000818:Animals; D002452:Cell Count; D002465:Cell Movement; D016039:Corneal Transplantation; D006085:Graft Survival / Q000276:immunology; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007108:Immune Tolerance / Q000187:drug effects*; D053590:Interleukin 1 Receptor Antagonist Protein; D007519:Isoantigens / Q000276:immunology*; D007801:Langerhans Cells / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009883:Ophthalmic Solutions; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*; D012795:Sialoglycoproteins / Q000008:administration & dosage / Q000494:pharmacology*; D016038:Skin Transplantation / Q000276:immunology; D014184:Transplantation, Homologous
C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D007519:Isoantigens; D009883:Ophthalmic Solutions; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins