title: Efficacy of topical blockade of interleukin-1 in experimental dry eye disease.
abstract: OBJECTIVE
  To evaluate the therapeutic efficacy of topical interleukin-1 receptor antagonist (IL-1Ra) in the treatment of dry eye disease.
  
  
  METHODS
  Laboratory investigation.
  
  
  METHODS
  Dry eye disease was induced in C57BL/6 female mice through exposure to a desiccating environment within a controlled environment chamber. Topical formulations containing 5% IL-1Ra, 1% methylprednisolone, 0.05% cyclosporin A, and a vehicle control containing carboxymethylcellulose sodium were applied after the induction of dry eye. Corneal fluorescein staining was performed by a masked observer in the different treatment groups. Immunohistochemical studies were undertaken to enumerate corneal CD11b+ cells, as well as to evaluate corneal lymphangiogenesis. Real-time polymerase reaction was used to quantify the expression of interleukin-1β in the cornea.
  
  
  RESULTS
  A significant decrease in corneal fluorescein staining was observed after topical treatment with 5% IL-1Ra (P < .01), 1% methylprednisolone (P < .01), and 0.05% cyclosporin A (P < .03). Additionally, a significant decrease in the numbers of central corneal CD11b+ cells (P < .05), corneal lymphatic growth (P < .05), and corneal interleukin-1β expression (P < .003), compared with vehicle treated, were demonstrated only after treatment with 5% IL-1Ra and 1% methylprednisolone, and were absent after cyclosporin A treatment.
  
  
  CONCLUSIONS
  Topical treatment with IL-1Ra is effective in ameliorating the clinical signs of the dry eye disease, as well as in reducing underlying inflammation. These effects are comparable with those resulting from treatment with topical methylprednisolone. Topical IL-1Ra may hold promise as a novel therapeutic strategy in the treatment of dry eye.
authors.affiliation: Schepens Eye Research Institute and Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Andre
authors.initials: A
authors.lastname: Okanobo
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Chauhan
authors.forename: Mohammad H
authors.initials: MH
authors.lastname: Dastjerdi
authors.forename: Shilpa
authors.initials: S
authors.lastname: Kodati
authors.forename: Reza
authors.initials: R
authors.lastname: Dana
mesh_terms: D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism; D016572:Cyclosporine / Q000627:therapeutic use; D004195:Disease Models, Animal; D015352:Dry Eye Syndromes / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D015590:Fluorophotometry; D005938:Glucocorticoids / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D053590:Interleukin 1 Receptor Antagonist Protein / Q000627:therapeutic use*; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D042583:Lymphangiogenesis / Q000187:drug effects; D042601:Lymphatic Vessels / Q000378:metabolism; D008775:Methylprednisolone / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL; D009883:Ophthalmic Solutions; D060888:Real-Time Polymerase Chain Reaction; D016896:Treatment Outcome
chemical_list: D039481:CD11b Antigen; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; D009883:Ophthalmic Solutions; D016572:Cyclosporine; D008775:Methylprednisolone