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Role of IL-12 and IFN- in Pseudomonas aeruginosa Corneal Infection

From the Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, Michigan.

PURPOSE. In Pseudomonas aeruginosa ocular infection, T-helper cell 1–responsive mouse strains are susceptible (the cornea perforates), and neutralization of IFN- before infection has been shown to delay the onset of perforation. IFN- is the predominant cytokine induced by IL-12, and positive regulation of IL-12 by IFN-, 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- production and the susceptibility phenotype.

RESULTS. To directly test the effect of IL-12 on IFN- 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- mRNA levels in the cornea and cervical lymph nodes and decreased TNF- 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- production and in the absence of the cytokine, both IFN- and TNF- levels in cornea are significantly decreased, resulting in unchecked bacterial growth and perforation.

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