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From the Department of Pathology, Dartmouth Medical School, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire
Brain abscess represents the infectious disease sequelae associated
with the influx of inflammatory cells and activation of resident
parenchymal cells in the central nervous system. However, the
immune response leading to the establishment of a brain abscess remains
poorly defined. In this study, we have characterized cytokine
and chemokine expression in an experimental brain abscess model in the
rat during the acute stage of abscess development. RNase protection
assay revealed the induction of the proinflammatory cytokines
interleukin (IL)-1
, IL-1ß, IL-6, and tumor
necrosis factor-
as early as 1 to 6 hours after
Staphylococcus aureus exposure. Evaluation of chemokine
expression by reverse transcription-polymerase chain reaction
demonstrated enhanced levels of the CXC chemokine KC 24 hours after
bacterial exposure, which correlated with the appearance of
neutrophils in the abscess. In addition, two CC
chemokines, monocyte chemoattractant protein-1 and
macrophage inflammatory protein-1
were induced within 24
hours after S. aureus exposure and preceded the influx
of macrophages and lymphocytes into the brain. Analysis of abscess
lesions by in situ hybridization identified CD11b+ cells
as the source of IL-1ß in response to S. aureus. Both
intercellular adhesion molecule-1 and platelet endothelial cell
adhesion molecule expression were enhanced on microvessels in
S. aureus but not sterile bead-implanted tissues
at 24 and 48 hours after treatment. These results characterize
proinflammatory cytokine and chemokine expression during the early
response to S. aureus in the brain and provide the
foundation to assess the functional significance of these mediators in
brain abscess pathogenesis.
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