Efficacy of topical blockade of interleukin-1 in experimental dry eye disease

Am J Ophthalmol. 2012 Jul;154(1):63-71. doi: 10.1016/j.ajo.2012.01.034. Epub 2012 Apr 26.


Purpose: To evaluate the therapeutic efficacy of topical interleukin-1 receptor antagonist (IL-1Ra) in the treatment of dry eye disease.

Design: 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • CD11b Antigen / metabolism
  • Cyclosporine / therapeutic use
  • Disease Models, Animal*
  • Dry Eye Syndromes / diagnosis
  • Dry Eye Syndromes / drug therapy*
  • Dry Eye Syndromes / genetics
  • Female
  • Fluorescent Antibody Technique, Indirect
  • Fluorophotometry
  • Glucocorticoids / therapeutic use
  • Immunosuppressive Agents / therapeutic use
  • Interleukin 1 Receptor Antagonist Protein / therapeutic use*
  • Interleukin-1beta / antagonists & inhibitors*
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Lymphangiogenesis / drug effects
  • Lymphatic Vessels / metabolism
  • Methylprednisolone / therapeutic use
  • Mice
  • Mice, Inbred C57BL
  • Ophthalmic Solutions
  • Real-Time Polymerase Chain Reaction
  • Treatment Outcome


  • CD11b Antigen
  • Glucocorticoids
  • Immunosuppressive Agents
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1beta
  • Ophthalmic Solutions
  • Cyclosporine
  • Methylprednisolone