Effect of metalloproteinase inhibitor on corneal cytokine expression afteralkali injury

PURPOSE. Interleukin (IL)-1 alpha and IL-6 levels in the cornea are greatly elevated during the early stages after an alkali burn in mice. The authors investigated the effect of synthetic inhibitor of matric metalloproteinase (SIMP) on the expression of inflammatory cytokines in alkali-burned murine corneas and evaluated the clinical appearance of the eyes. METHODS. After 0.5N NaOH-alkali burns to 400 corneas of ICR mice, 200 recei ved 400 mu g/ml of SIMP topically 4 times a day while 200 corneas were simi larly treated with vehicle only. At days 4, 7 and 14 after injury, each cor nea was assigned a clinical score for corneal opacity, corneal epithelial d efect, hyphema and cataract. Extracts of injured corneas in each group were then assayed for cytokine production using ELISA systems for IL-1 alpha, I L-1 beta, IL-6 and tumor necrosis factor-alpha (TNF-alpha). RESULTS. The levels of IL-1 alpha IL-1 beta and IL-6 were significantly low er in the SIMP-treated group than in the vehicle-treated group 7 days after the burn. However, levels of these cytokines were similar in the SIMP and non-SIMP groups at days 4 and 14. Levels of TNF-alpha did not differ betwee n both groups at any postinjury time. in the SIMP-treated corneas, there wa s less opacification and hyphema formation and epithelial regeneration was faster. CONCLUSIONS. Topical application of SIMP in alkali-burned murine corneas re duced the expression of IL-1 alpha, IL-1 beta, and IL-6 and lessened the se verity of the injury.