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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Dekaris
I J
IJ
Harvard Medical School, Schepens Eye Research Institute, Laboratory of Immunology, Boston, MA 02114, USA.
Yamada
J J
JJ
Streilein
W J
WJ
Dana
R M
RM
D000287:Administration, Topical; D000818:Animals; D016039:Corneal Transplantation; D006085:Graft Survival / Q000187:drug effects*; D006649:Histocompatibility Antigens / Q000276:immunology; D007114:Immunization; D053590:Interleukin 1 Receptor Antagonist Protein; D007519:Isoantigens / Q000276:immunology; D008285:Major Histocompatibility Complex / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D015778:Minor Histocompatibility Antigens / Q000276:immunology; D012795:Sialoglycoproteins / Q000494:pharmacology*; D014184:Transplantation, Homologous
D006649:Histocompatibility Antigens; C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D007519:Isoantigens; D015778:Minor Histocompatibility Antigens; D012795:Sialoglycoproteins