Local suppression of IL-1 by receptor antagonist in the rat model of corneal alkali injury

Exp Eye Res. 2003 Feb;76(2):161-7. doi: 10.1016/s0014-4835(02)00293-2.


Proinflammatory cytokines, including interleukin-1 (IL-1) have been implicated in the inflammation that follows corneal alkali injury. The purpose of this series of experiments was to test whether topically applied interleukin-1 receptor antagonist (IL-1ra) could suppress corneal inflammation and promote transparency after alkali injury. Alkali injury was induced on day 0 by application of 1N NaOH to both eyes of Wistar rats (n = 28). Immediately thereafter, eyes received either topical IL-1ra (20 mg ml(-1)) in 0.2% sodium hyaluronate or vehicle alone three times daily during days 0-14. Biomicroscopic features including corneal opacity and neovascularization were assessed using a standard grading scheme. Inflammation was quantified histologically. Corneas excised at day 3 and 7 (randomly selected six eyes in each group per time point studied) were homogenized, and levels of IL-1alpha, IL-1beta, IL-6, IL-8, IL-10, and RANTES were quantified by enzyme-linked immunosorbent assay. Epithelial wound healing was examined by computed analysis of fluorescein stained corneal photographs taken daily until day 14. According to these evaluations, eyes treated with IL-1ra maintained corneal transparency with minimal neovascular invasion. Additionally, corneal damage and cell infiltration were reduced on day 7 (infiltration cells were almost 40% decreased). All cytokine/chemokine levels in IL-1ra treated eyes were significantly lower at day 3, and IL-6 and IL-10 remained significantly lower at day 7 compared to vehicle-treated eyes. IL-1ra treatment retarded epithelial wound healing in the early stage (day 1-4); however, subsequently IL-1ra treated eyes had enhanced healing with full epithelial closure at nearly the same time point as vehicle-treated eyes (day 10). We conclude that local antagonism of IL-1 after alkali injury can significantly decrease corneal inflammation and lead to enhanced corneal transparency.

MeSH terms

  • Animals
  • Burns, Chemical / complications*
  • Cornea / metabolism
  • Corneal Opacity / prevention & control
  • Disease Models, Animal
  • Eye Burns / chemically induced
  • Eye Burns / complications*
  • Female
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1 / metabolism*
  • Interleukins / metabolism
  • Keratitis / etiology
  • Keratitis / pathology
  • Keratitis / prevention & control*
  • Rats
  • Rats, Wistar
  • Receptors, Interleukin-1 / antagonists & inhibitors
  • Recombinant Proteins / therapeutic use
  • Sialoglycoproteins / therapeutic use*
  • Sodium Hydroxide
  • Wound Healing / drug effects


  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1
  • Interleukins
  • Receptors, Interleukin-1
  • Recombinant Proteins
  • Sialoglycoproteins
  • Sodium Hydroxide