A protective role for IL-6 in staphylococcal microbial keratitis.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Hume
Emma B H
EB
The School of Optometry and Vision Science, The University of New South Wales, Kensington, NSW 2052, Australia. e.hume@ier.org.au
Cole
Nerida
N
Garthwaite
Linda L
LL
Khan
Shamila
S
Willcox
Mark D P
MD
D000818:Animals; D018925:Chemokines / Q000378:metabolism; D015169:Colony Count, Microbial; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D015818:Eye Infections, Bacterial / Q000378:metabolism / Q000382:microbiology / Q000517:prevention & control*; D015850:Interleukin-6 / Q000008:administration & dosage / Q000502:physiology*; D007634:Keratitis / Q000378:metabolism / Q000382:microbiology* / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000502:physiology; D009195:Peroxidase / Q000378:metabolism; D011994:Recombinant Proteins / Q000008:administration & dosage; D013203:Staphylococcal Infections / Q000378:metabolism / Q000382:microbiology / Q000517:prevention & control*; D013211:Staphylococcus aureus / Q000472:pathogenicity
D018925:Chemokines; D016207:Cytokines; D015850:Interleukin-6; D011994:Recombinant Proteins; D009195:Peroxidase