Pseudomonas aeruginosa keratitis in IL-6-deficient mice.
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.
Cole
Nerida
N
Co-operative Research Centre for Eye Research and Technology, Cornea and Contact Lens Research Unit and School of Optometry, University of New South Wales, Sydney, Australia.
Bao
Shisan
S
Stapleton
Fiona
F
Thakur
Archana
A
Husband
Alan J
AJ
Beagley
Kenneth W
KW
Willcox
Mark D P
MD
D000818:Animals; D018925:Chemokines / Q000096:biosynthesis / Q000276:immunology; D003176:Complement C3 / Q000096:biosynthesis / Q000276:immunology; D006651:Histocytochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000172:deficiency* / Q000276:immunology; D007634:Keratitis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology; D011552:Pseudomonas Infections / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D011550:Pseudomonas aeruginosa / Q000276:immunology*; D013047:Specific Pathogen-Free Organisms
D018925:Chemokines; D003176:Complement C3; D015850:Interleukin-6; D018799:Intercellular Adhesion Molecule-1