A Protective Role for IL-6 in Staphylococcal Microbial Keratitis

• Published in: Investigative ophthalmology & visual science Vol. 47; no. 11; pp. 4926 - 4930
• Main Authors: Hume, Emma B. H, Cole, Nerida, Garthwaite, Linda L, Khan, Shamila, Willcox, Mark D. P
• Format: Journal Article
• Language: English
• Published: Rockville, MD ARVO 01.11.2006; Association for Research in Vision and Ophtalmology
• Subjects: Animals; Biological and medical sciences; Chemokines - metabolism; Colony Count, Microbial; Cytokines - metabolism; Diseases of cornea, anterior segment and sclera; Enzyme-Linked Immunosorbent Assay; Eye and associated structures. Visual pathways and centers. Vision; Eye Infections, Bacterial - metabolism; Eye Infections, Bacterial - microbiology; Eye Infections, Bacterial - prevention & control; Fundamental and applied biological sciences. Psychology; Interleukin-6 - administration & dosage; Interleukin-6 - physiology; Keratitis - metabolism; Keratitis - microbiology; Keratitis - prevention & control; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Knockout; Neutrophils - physiology; Ophthalmology; Peroxidase - metabolism; Recombinant Proteins - administration & dosage; Staphylococcal Infections - metabolism; Staphylococcal Infections - microbiology; Staphylococcal Infections - prevention & control; Staphylococcus aureus - pathogenicity; Vertebrates: nervous system and sense organs; Keratitis; Keratopathy; Staphylococcus; Infection; Interleukin 6; Prevention; Eye disease; Bacteriosis; Bacteria; Micrococcales; Micrococcaceae; Ophthalmology; Staphylococcal infection; Anterior segment disease
• ISSN: 0146-0404; 1552-5783; 1552-5783
• DOI: 10.1167/iovs.06-0340

To determine whether interleukin-6 (IL-6) plays a protective role in Staphylococcus aureus keratitis in a gene knockout (gko) mouse model and to determine whether IL-6 may be used as a therapy to modulate host responses and control bacterial infection, thereby reducing scarring. The eyes of IL-6 gko mice and wild-type mice were challenged topically with S. aureus and examined at 24 hours after infection. Keratitis was examined clinically and histologically. Bacterial and polymorphonuclear leukocytes (PMNs) were enumerated, and cytokine and chemokine levels were determined by ELISA. Exogenous IL-6 was administered to both IL-6 gko and wild-type mice, and clinical parameters were determined. IL-6 gko mice showed more severe disease, with increased bacterial counts and PMNs, than did wild-type mice. Changes in levels of chemokines and cytokines were also observed. Administration of exogenous IL-6 resulted in an improved outcome in IL-6 gko mice, with a threefold reduction in bacterial load. The data suggest an important regulatory role for IL-6 in modulating excessive inflammatory responses and in controlling bacterial proliferation. IL-6 may play a role in the priming and activation of neutrophils. It could represent a broad-spectrum therapy to improve outcomes in patients who have these potentially blinding infections.