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

• Published in: Experimental eye research 2003-02, Vol.76 (2), p.161-167
• Main Authors: Yamada, Jun, Reza Dana, M., Sotozono, Chie, Kinoshita, Shigeru
• Format: Article
• Language: English
• Subjects: alkali burns; Animals; Biological and medical sciences; Burns, Chemical - complications; Cornea - metabolism; Corneal Opacity - prevention & control; corneal wound healing; cytokine; Disease Models, Animal; Diseases of cornea, anterior segment and sclera; Eye Burns - chemically induced; Eye Burns - complications; Female; interleukin; Interleukin 1 Receptor Antagonist Protein; Interleukin-1 - metabolism; Interleukins - metabolism; Keratitis - etiology; Keratitis - pathology; Keratitis - prevention & control; Medical sciences; neovascularization; Ophthalmology; Rats; Rats, Wistar; Receptors, Interleukin-1 - antagonists & inhibitors; Recombinant Proteins - therapeutic use; Sialoglycoproteins - therapeutic use; Sodium Hydroxide; Wound Healing - drug effects
• ISSN: 0014-4835; 1096-0007
• 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-1α, IL-1β, 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.