title: 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.
authors.affiliation: 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.
authors.forename: Nerida
authors.initials: N
authors.lastname: Cole
authors.forename: Shisan
authors.initials: S
authors.lastname: Bao
authors.forename: Fiona
authors.initials: F
authors.lastname: Stapleton
authors.forename: Archana
authors.initials: A
authors.lastname: Thakur
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Husband
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Beagley
authors.forename: Mark D P
authors.initials: MD
authors.lastname: Willcox
mesh_terms: 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
chemical_list: D018925:Chemokines; D003176:Complement C3; D015850:Interleukin-6; D018799:Intercellular Adhesion Molecule-1