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

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 × 104 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-1α and IL-1β 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.