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EA Szliter, X Huang, R Barrett, L Hazlett; Response to P.aeruginosa Corneal Infection in IL-1ß-Converting Enzyme-deficient Mice . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1593.
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Purpose: IL-1ß-converting enzyme (ICE) cleaves pro-IL-1ß to the mature, released form. Although other proteases can process pro-IL-1ß, ICE-deficient (ICE -/-) mice do not release mature IL-1ß in response to endotoxin. The purpose of our study was to investigate the response of ICE -/- mice in an in vivo model of bacterial induced inflammation. Methods: Mean clinical scores, slit lamp, histopathology and ELISA analysis were used to characterize the response of ICE -/- vs. C57BL/6 (B6) mice after ocular bacterial infection. Results: Significant differences in mean clinical scores, indicative of disease severity, were observed in B6 vs. ICE -/- mice at 1, 2, 3, and 5 days p.i. (P=0.0001, 0.002, 0.0001, 0.0001, respectively). The decreased inflammatory response in ICE -/- mice was particularly striking at 1 day p.i. and both slit lamp and histopathology (cellular infiltrate decreased) confirmed the visual scoring of less severe disease in the -/- mice vs. perforation in the B6 animals. ELISA analysis also was used and revealed significantly decreased protein levels of IL-1ß (46.5%), MIP-2 (54.1%), IL-6 (60%), and IL-18 (25.8%), at 1 day p.i. (P=0.001, 0.001, 0.0003, and 0.04, respectively), which remained decreased or at similar levels (only IL-18) at 3 and 5 days p.i. in the cornea of ICE -/- vs. B6 mice. IFN-γ protein levels in cornea also were tested for, but not detected, by ELISA. Conclusion: These data provide evidence that in the endogenous absence of IL-1ß-converting enzyme, less inflammation was induced after bacterial challenge and this was correlated with reduced levels of several proinflammatory cytokines and chemokines in the cornea of ICE -/- vs. B6 mice. Support: Vertex Pharmaceuticals Inc., Cambridge MA, and in part by NIH EY02986 and P30EY04068.
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