Abstract
The fatality rate associated with Streptococcus pneumoniae meningitis remains high despite adequate antibiotic treatment. IL-1 is an important proinflammatory cytokine, which is up-regulated in brain tissue after the induction of meningitis. To determine the role of IL-1 in pneumococcal meningitis we induced meningitis by intranasal inoculation with 8 x 10(4) CFU of S. pneumoniae and 180 U of hyaluronidase in IL-1R type I gene-deficient (IL-1R(-/-)) mice and wild-type mice. Meningitis resulted in elevated IL-1alpha and IL-1beta mRNA and protein levels in the brain. The absence of an intact IL-1 signal was associated with a higher susceptibility to develop meningitis. Furthermore, the lack of IL-1 impaired bacterial clearance, as reflected by an increased number of CFU in cerebrospinal fluid of IL-1R(-/-) mice. The characteristic pleocytosis of meningitis was not significantly altered in IL-1R(-/-) mice, but meningitis was associated with lower brain levels of cytokines. The mortality was significantly higher and earlier in the course of the disease in IL-1R(-/-) mice. These results demonstrate that endogenous IL-1 is required for an adequate host defense in pneumococcal meningitis.
MeSH terms
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Animals
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Brain / immunology
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Brain / metabolism
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Brain / pathology
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Cerebrospinal Fluid / immunology
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Cerebrospinal Fluid / microbiology
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Cytokines / biosynthesis
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Genetic Predisposition to Disease
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Immunity, Innate / genetics
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Interleukin 1 Receptor Antagonist Protein
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Interleukin-1 / biosynthesis
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Leukocytosis / cerebrospinal fluid
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Leukocytosis / genetics
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Leukocytosis / immunology
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Leukocytosis / microbiology
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Meningitis, Pneumococcal / genetics*
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Meningitis, Pneumococcal / immunology*
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Meningitis, Pneumococcal / mortality
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Meningitis, Pneumococcal / pathology
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Receptors, Interleukin-1 / antagonists & inhibitors
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Receptors, Interleukin-1 / deficiency*
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Receptors, Interleukin-1 / genetics*
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Receptors, Interleukin-1 / physiology
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Receptors, Interleukin-1 Type I
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Sialoglycoproteins / biosynthesis
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Signal Transduction / genetics
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Signal Transduction / immunology
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Streptococcus pneumoniae / growth & development
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Streptococcus pneumoniae / immunology
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Survival Analysis
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Up-Regulation / genetics
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Up-Regulation / immunology
Substances
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Cytokines
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Il1rn protein, mouse
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Interleukin 1 Receptor Antagonist Protein
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Interleukin-1
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Receptors, Interleukin-1
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Receptors, Interleukin-1 Type I
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Sialoglycoproteins