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Linda D. Hazlett, Xiaowen L. Rudner, Sharon A. McClellan, Ronald P. Barrett, Shahrzad Lighvani; Role of IL-12 and IFN-γ in Pseudomonas aeruginosa Corneal Infection. Invest. Ophthalmol. Vis. Sci. 2002;43(2):419-424.
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purpose. In Pseudomonas aeruginosa ocular infection, T-helper
cell 1–responsive mouse strains are susceptible (the cornea
perforates), and neutralization of IFN-γ before infection has been
shown to delay the onset of perforation. IFN-γ is the predominant
cytokine induced by IL-12, and positive regulation of IL-12 by IFN-γ,
if unchecked, leads to excessive cytokine production and toxicity.
Despite its potential importance, the role of IL-12 in ocular infection
with P. aeruginosa remains unexplored and was the
purpose of this study.
methods. IL-12 knockout mice, histopathology, RT/PCR and ELISA analyses,
immunocytochemistry, and quantitation of viable bacteria in cornea were
used to examine the role of IL-12 in IFN-γ production and the
results. To directly test the effect of IL-12 on IFN-γ production, IL-12
knockout and wild-type C57BL/6 mice were used. Both groups of mice were
susceptible to infection, with corneal perforation seen at 5 to 7 days
after infection. RT-PCR and ELISA analyses confirmed that IL-12 message
and protein levels were elevated after infection only in the wild-type
mouse cornea. Other differences between the two groups were detected.
Knockout versus wild-type mice showed a significant decrease in IFN-γ
mRNA levels in the cornea and cervical lymph nodes and decreased
TNF-α protein levels in cornea. Corneas of knockout mice also had a
significant increase in bacterial load at 5 days after infection when
compared with wild-type mice.
conclusions. These data provide evidence that IL-12 is important in IFN-γ
production and in the absence of the cytokine, both IFN-γ and TNF-α
levels in cornea are significantly decreased, resulting in unchecked
bacterial growth and perforation.
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