title: Local suppression of IL-1 by receptor antagonist in the rat model of corneal alkali injury.
abstract: 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.
authors.affiliation: Department of Ophthalmology, Kyoto Prefectural University of Medicine, 465 Kajiicho Hirokoji-agaru Kawaramachi-dori, Kamigyo-ku, Kyoto 602-0841, Japan. jyamada@ophth.kpu-m.ac.jp
authors.forename: Jun
authors.initials: J
authors.lastname: Yamada
authors.forename: M Reza
authors.initials: MR
authors.lastname: Dana
authors.forename: Chie
authors.initials: C
authors.lastname: Sotozono
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kinoshita
mesh_terms: D000818:Animals; D002057:Burns, Chemical / Q000150:complications*; D003315:Cornea / Q000378:metabolism; D003318:Corneal Opacity / Q000517:prevention & control; D004195:Disease Models, Animal; D005126:Eye Burns / Q000139:chemically induced / Q000150:complications*; D005260:Female; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000378:metabolism*; D007378:Interleukins / Q000378:metabolism; D007634:Keratitis / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D011994:Recombinant Proteins / Q000627:therapeutic use; D012795:Sialoglycoproteins / Q000627:therapeutic use*; D012972:Sodium Hydroxide; D014945:Wound Healing / Q000187:drug effects
chemical_list: D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D007378:Interleukins; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins; D012795:Sialoglycoproteins; D012972:Sodium Hydroxide