Pseudomonas aeruginosa keratitis in IL-6-deficient mice.

ABSTRACT

BACKGROUND: Pseudomonas aeruginosa infection is one of the most destructive diseases of the eye. The host response to this infection is critical to the outcome. Interleukin-6 (IL-6) is implicated in this response; however, the mechanisms by which IL-6 contributes to the host defences in corneal infection remain unclear. Using IL-6-/- mice, we have explored the role of IL-6 in P. aeruginosa keratitis. METHODS: The eyes of IL-6 gene knockout and wild-type mice were challenged topically with P. aeruginosa and examined on days 1-7. Keratitis was examined clinically and histologically. Cytokine, chemokine and complement 3 levels were determined by ELISA and ICAM-1 by immunohistochemistry. RESULTS: Clinically, the IL-6-/- mice showed more severe disease than wild-type mice and this was supported by the histological findings. More than 2-fold higher bacterial load was detected in the eyes of the IL-6-/- mice than in those of the wild-type mice. Neutrophil infiltration to the central cornea of the IL-6-/- mice failed to occur in response to infection, although a greater number of neutrophils were present in the whole eye. This may in part be due to the reduced expression of the adhesion molecule ICAM-1 in the cornea, but does not appear to stem from insufficient production of chemokines or complement 3. CONCLUSIONS: Our findings indicate that IL-6 is critical to the host defence of the cornea during P. aeruginosa infection. Pharmacological manipulation of the IL-6 response may represent a rational strategy for new interventions.