Topical interleukin 1 receptor antagonist promotes corneal transplant survival.
BACKGROUND
Interleukin (IL)-1 is a potent proinflammatory cytokine that plays a critical role in initiating and maintaining immunogenic inflammation. We performed a series of experiments to determine whether the topical application of IL-1 receptor antagonist (IL-1ra) can prolong corneal transplant survival in the murine model of orthotopic allotransplantation.


METHODS
For all experiments, C57BL/6 corneas were transplanted into BALB/c (major histocompatibility and minor histocompatibility-disparate) eyes. "High-risk" transplants were transplants that had been sutured into BALB/c recipient beds with corneal neovascularization induced by placement of three interrupted sutures in the host cornea 2 weeks earlier. Both risk groups were divided in a masked fashion into treatment subgroups that received either 20 mg/ml of IL-1ra mixed in 0.2% sodium hyaluronate vehicle (n=28) or placebo alone (n=25). All transplants were evaluated for 8 weeks after surgery for signs of rejection. At the end of follow-up, corneal specimens were processed for enumeration of Langerhans cells and histopathological evaluation.


RESULTS
Survival rates of both normal-risk and high-risk transplants increased significantly among the IL-1ra-treated animals compared with untreated controls by both stratified Mantel-Haenszel (P=0.02) and Kaplan-Meier survival (P=0.03) analyses. Furthermore, both normal- and high-risk IL-1ra-treated grafts had significantly less inflammation and Langerhans cells infiltration compared with untreated controls.


CONCLUSIONS
Topical treatment with IL-1ra has a significantly positive effect in promoting corneal allograft survival.
Dana
M R
MR
Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts 02114, USA.
Yamada
J
J
Streilein
J W
JW
D000287:Administration, Topical; D000818:Animals; D003315:Cornea / Q000098:blood supply / Q000166:cytology; D016039:Corneal Transplantation / Q000276:immunology*; D006085:Graft Survival / Q000187:drug effects; D053590:Interleukin 1 Receptor Antagonist Protein; D007634:Keratitis / Q000188:drug therapy / Q000473:pathology; D007801:Langerhans Cells / Q000166:cytology; D051379:Mice; D008807:Mice, Inbred BALB C; D018919:Neovascularization, Physiologic; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D011994:Recombinant Proteins / Q000494:pharmacology; D012795:Sialoglycoproteins / Q000494:pharmacology*
C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins; D012795:Sialoglycoproteins