Interleukin-1 receptor antagonist suppresses Langerhans cell activity and promotes ocular immune privilege.
OBJECTIVE
To determine whether the capacity of Langerhans cells (LCs) to abrogate ocular immune privilege can be suppressed by the topical application of interleukin-1 receptor antagonist (IL-1ra).


METHODS
Cautery was applied to corneas of BALB/c mice on day 0 to induce centripetal migration of LCs. Immune privilege was tested by the ability to induce anterior chamber-associated immune deviation (ACAID) to intracamerally injected soluble antigen 1 to 2 weeks after cautery application. The number of LCs was enumerated by immunofluorescent staining. In other experiments, freshly procured Thy-1-depleted epidermal cells, with or without LC depletion, were injected directly into virgin murine corneas before testing for ACAID. All test animals were randomized for treatment with either topical IL-1ra or placebo in a masked fashion for 1 to 2 weeks after induction of LC migration and before intracameral injection of antigen.


RESULTS
Intracorneal injection of freshly procured LC-depleted epidermal cells into normal eyes failed to abrogate ACAID, whereas LC-containing cell populations uniformly led to loss of immune privilege (P < 0.01). Topical treatment with IL-1ra led to retention of the cauterized eyes' capacity for ACAID induction (P < 0.01) and to a profound (>80%) suppression of LC migration compared with untreated controls (P < 0.01). Additionally, topical IL-1ra treatment of eyes with intracorneally injected LCs preserved immune privilege and ACAID induction (P < 0.001).


CONCLUSIONS
IL-1 mediates mechanisms of immunity in corneal inflammation that subvert the normal eye's immune privileged state. However, its antagonism with topical administration of IL-1ra preserves ocular immune privilege and ACAID through suppression of LC function.
Dana
M R
MR
Schepens Eye Research Institute, and the Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts 02114, USA.
Dai
R
R
Zhu
S
S
Yamada
J
J
Streilein
J W
JW
D000287:Administration, Topical; D000818:Animals; D000867:Anterior Chamber / Q000276:immunology*; D002465:Cell Movement / Q000187:drug effects; D003315:Cornea / Q000276:immunology*; D004564:Electrocoagulation; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D007108:Immune Tolerance; D007109:Immunity; D007165:Immunosuppression Therapy; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000276:immunology; D015603:Keratinocytes / Q000276:immunology; D007801:Langerhans Cells / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*; D012795:Sialoglycoproteins / Q000008:administration & dosage*
C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins; D010047:Ovalbumin