INTERLEUKIN-1 RECEPTOR ANTAGONIST SUPPRESSES LANGERHANS CELL-ACTIVITYAND PROMOTES OCULAR IMMUNE PRIVILEGE

PURPOSE. To determine whether the capacity of Langerhans cells (LCs) t o abrogate ocular immune privilege can be suppressed by the topical ap plication of interleukin-1 receptor antagonist (IL-1ra). METHODS. Caut ery was applied to corneas of BALB/c mice on day 0 to induce centripet al migration of LCs. Immune privilege was tested by the ability to ind uce anterior chamber-associated immune deviation (ACAID) to intracamer ally injected soluble antigen 1 to 2 weeks after cautery application. The number of LCs was enumerated by immunofluorescent staining. In oth er experiments, freshly procured Thy-1-depleted epidermal cells, with or without LC depletion, were injected directly into virgin murine cor neas before testing for ACAID. All test animals were randomized for tr eatment with either topical IL-1ra or placebo in a masked fashion for 1 to 2 weeks after induction of LC migration and before intracameral i njection of antigen. RESULTS. Intracorneal injection of freshly procur ed LC-depleted epidermal cells into normal eyes failed to abrogate ACA ID, whereas LC-containing cell populations uniformly led to loss of im mune privilege (P < 0.01). Topical treatment with IL-1ra led to retent ion of the cauterized eyes' capacity for ACAID induction (P < 0.01) an d to a profound (>80%) suppression of LC migration compared with untre ated controls (P < 0.01). Additionally, topical IL-1ra treatment of ey es with intracorneally injected LCs preserved immune privilege and ACA ID induction (P < 0.001). CONCLUSIONS. IL-1 mediates mechanisms of imm unity in corneal inflammation that subvert the normal eye's immune pri vileged state. However, its antagonism with topical administration of IL-1ra preserves ocular immune privilege and ACAID through suppression of LC function.