IL-1 receptor type 1 gene-deficient mice demonstrate an impaired host defense against pneumococcal meningitis

Petra J. G. Zwijnenburg, Tom van der Poll, Sandrine Florquin, John J. Roord, A. Marceline van Furth

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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 languageEnglish
Pages (from-to)4724-4730
Number of pages7
JournalJournal of immunology (Baltimore, Md.
Issue number9
Publication statusPublished - 1 May 2003


  • 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

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