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 8x10(4) CFU of S. pneumoniae and 180 U of hyaluronidase in IL-1R type I gene-deficient (IL-IR-/-) 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
Original language | English |
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Pages (from-to) | 4724-4730 |
Number of pages | 7 |
Journal | Journal of immunology (Baltimore, Md. |
Volume | 170 |
Issue number | 9 |
DOIs | |
Publication status | Published - 1 May 2003 |
Keywords
- Animals
- Brain/immunology
- Cerebrospinal Fluid/immunology
- Cytokines/biosynthesis
- Genetic Predisposition to Disease
- Immunity, Innate/genetics
- Interleukin 1 Receptor Antagonist Protein
- Interleukin-1/biosynthesis
- Leukocytosis/cerebrospinal fluid
- Meningitis, Pneumococcal/genetics
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Receptors, Interleukin-1 Type I
- Receptors, Interleukin-1/antagonists & inhibitors
- Sialoglycoproteins/biosynthesis
- Signal Transduction/genetics
- Streptococcus pneumoniae/growth & development
- Survival Analysis
- Up-Regulation/genetics