title: Interleukin-1 receptor antagonist suppresses Langerhans cell activity and promotes ocular immune privilege.
abstract: 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.
authors.affiliation: Schepens Eye Research Institute, and the Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts 02114, USA.
authors.forename: M R
authors.initials: MR
authors.lastname: Dana
authors.forename: R
authors.initials: R
authors.lastname: Dai
authors.forename: S
authors.initials: S
authors.lastname: Zhu
authors.forename: J
authors.initials: J
authors.lastname: Yamada
authors.forename: J W
authors.initials: JW
authors.lastname: Streilein
mesh_terms: 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*
chemical_list: C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins; D010047:Ovalbumin