Contribution of the cornea to cytokine levels in the whole eye induced during the early phase of Pseudomonas aeruginosa challenge

Abstract

Pseudomonas aeruginosa keratitis is one of the most destructive diseases of the cornea. The host response to this infection is critical to the outcome, and is regulated by cytokines produced in the ocular tissue. In this study, we assessed the relative contribution of the cytokines produced in the cornea to the inflammatory response of the whole eye to gain a better understanding of the inflammatory and regulatory processes in the ocular environment during localized corneal infection. C57BL/6 mice were challenged by topical application of P. aeruginosa to wounded corneas. Corneas and whole eyes were harvested 24 h post-challenge and bacterial numbers, myeloperoxidase levels and the levels of cytokines known to be important in keratitis were determined. The site of production of IL-6 and KC in the retina was determined by in situ hybridization. Before infection, 90% of macrophage inflammatory protein (MIP)-2 and approximately 80% of all IFN-gamma and IL-10 produced constitutively in the eye was found outside the cornea. Twenty-four hours after infection, bacterial numbers, levels of myeloperoxidase, and levels of MIP-2 and IL-1 were not different, whether measured in cornea or whole eye. However, expression of IL-6, KC, IFN-gamma and IL-10 was significantly greater in whole eyes than in the corneas of infected eyes. The cells expressing IL-6 and KC in the retina were identified by in situ hybridization. This study indicates that during corneal inflammation, the response of the whole eye as well as the cornea needs to be considered.