1. ¹Institute for Eye Research, Sydney, New South Wales, Australia
2. ²School of Optometry and Vision Science, The University of New South Wales, Sydney, New South Wales, Australia
3. ³Vision Cooperative Research Centre, Sydney, New South Wales, Australia
4. ⁴Faculty of Veterinary Science, The University of Sydney, Sydney, New South Wales, Australia

Correspondence: Dr E Hume, Institute for Eye Research, Rupert Myers Building, The University of New South Wales, Sydney, New South Wales 2052, Australia. E-mail:e.hume@ier.org.au

Received 31 July 2006; Revised 21 November 2006; Accepted 8 January 2007; Published online 27 March 2007.

Abstract

Interleukin-4 (IL-4) has previously been implicated in a protective response to Staphylococcus aureus corneal infection. Consequently, the specific role of IL-4 during S. aureus corneal infection was investigated using IL-4 gene knockout mice. The eyes of IL-4-/- mice and wild-type mice were challenged topically with S. aureus and examined at 24 h post-infection. Keratitis was examined clinically and histologically. Bacterial and polymorphonuclear leucocytes (PMN) numbers were enumerated and cytokine and chemokine levels determined by enzyme-linked immunosorbent assay. Exogenous IL-4 was administered to both IL-4-/- and wild-type mice and clinical parameters were determined. A lack of IL-4 resulted in a significant increase in clinical scores, pathology, bacterial load and neutrophil numbers. The absence of IL-4 also resulted in an upregulation of interferon (IFN)- and a downregulation of IL-6, IL-10 and the chemokines KC and macrophage inflammatory protein-2. Administration of exogenous IL-4 to IL-4-/- mice was protective but time-dependent. This study highlights the protective role of IL-4 during S. aureus infection and emphasizes the balance between IL-4 and IFN- in achieving bacterial control and maintaining the integrity of the cornea. This information may lead to the development of novel therapeutic strategies potentially improving the prognosis for infection of this unique avascular site.