Experimental Pseudomonas aeruginosa keratitis in interleukin-10 gene knockout mice.
Pseudomonas aeruginosa keratitis is one of the most destructive diseases of the cornea. The host response to this infection is critical to the outcome. The cytokine interleukin-10 (IL-10) is thought to play an important role in modulating excessive inflammation and antimicrobial defenses. We have found that in IL-10(-/-) mice there is a significant decrease in bacterial load in corneas at 7 days postchallenge with P. aeruginosa. This decrease was accompanied by a reduction in neutrophil numbers in the cornea and changes in cytokine levels compared to those of wild-type mice. A characteristic increase in neovascularization in the cornea was found in the IL-10(-/-) mice. This increased angiogenesis correlated with an increased expression of KC, whereas the kinetics of macrophage inflammatory peptide 2 expression correlated with neutrophil numbers. This finding suggests that KC may play a role in corneal angiogenesis. The source of IL-10 in mouse corneas was identified as a subpopulation of infiltrating cells and keratocytes. This study demonstrates that IL-10 plays an important role in regulating the balance of inflammatory mediators during P. aeruginosa infection of the cornea.
Cole
Nerida
N
Cooperative Research Center for Eye Research and Technology, University of New South Wales, Sydney, Australia.
Krockenberger
Mark
M
Stapleton
Fiona
F
Khan
Shamila
S
Hume
Emma
E
Husband
Alan J
AJ
Willcox
Mark
M
D000818:Animals; D018925:Chemokines / Q000032:analysis; D015169:Colony Count, Microbial; D016510:Corneal Neovascularization; D016207:Cytokines / Q000032:analysis; D007371:Interferon-gamma / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics / Q000502:physiology*; D007634:Keratitis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000502:physiology; D011552:Pseudomonas Infections / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D011550:Pseudomonas aeruginosa / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018925:Chemokines; D016207:Cytokines; D016753:Interleukin-10; D007371:Interferon-gamma