Purpose: 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.