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E. B. Hume, N. Cole, S. Khan, T. Schubert, L. L. Garthwaite, M. D. P. Willcox; The Role of Interleukin-4 in Pseudomonas aeruginosa and Staphylococcus aureus Corneal Infection. Invest. Ophthalmol. Vis. Sci. 2007;48(13):722.
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We have used IL-4 gene knockout mice to investigate the role of this complex inflammatory mediator during both Gram-positive and Gram-negative bacterial infection, which may lead to a better understanding of the cytokine response of the cornea, a unique avascular site, to infection caused by both P. aeruginosa and S. aureus
Corneas of 6-8 week old IL-4-/- and wild type mice were topically challenged with either P. aeruginosa (ATCC strain 19660: 2.0 x 106 cfu) or S. aureus (MK ulcer isolate Staph 38: 4.0 x 108 cfu). Eyes were harvested 24 hours post-challenge and bacterial numbers, myeloperoxidase levels were enumerated. Levels of IL-ß, MIP-2, KC, IFN-γ, IL-6 and IL-10 were assayed by ELISA.
When challenged with S.aureus, IL-4-/- mice showed a more severe response than wild type mice both clinically and histologically, with a corresponding 10-fold increase in bacterial load. During S. aureus infection, a significant increase in levels of the chemokines/cytokines IL-10, IL-6, KC and MIP-2 were observed in IL-4 -/- mice with a corresponding decrease in levels of IFN-γ. During challenge with P. aeruginosa no differences were observed clinically, histologically or in bacterial load between IL-4-/- and wild type mice. During challenge with P. aeruginosa levels of IL-6 increased in gko mice and IL-10 levels were decreased in gko mice.
Our data suggest that IL-4 may play an important protective or regulatory role during Gram-positive corneal infection. However, IL-4 may not be important in the outcome of Gram-negative corneal infection despite alteration in the cytokine response.
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