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 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.
Zwijnenburg
Petra J G
PJ
Department of Pediatrics, Vrije Universiteit Medical Center, Amsterdam, The Netherlands.
van der Poll
Tom
T
Florquin
Sandrine
S
Roord
John J
JJ
Van Furth
A Marceline
AM
D000818:Animals; D001921:Brain / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002555:Cerebrospinal Fluid / Q000276:immunology / Q000382:microbiology; D016207:Cytokines / Q000096:biosynthesis; D020022:Genetic Predisposition to Disease; D007113:Immunity, Innate / Q000235:genetics; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000096:biosynthesis; D007964:Leukocytosis / Q000134:cerebrospinal fluid / Q000235:genetics / Q000276:immunology / Q000382:microbiology; D008586:Meningitis, Pneumococcal / Q000235:genetics* / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D053573:Receptors, Interleukin-1 Type I; D012795:Sialoglycoproteins / Q000096:biosynthesis; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D013296:Streptococcus pneumoniae / Q000254:growth & development / Q000276:immunology; D016019:Survival Analysis; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
D016207:Cytokines; C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D053573:Receptors, Interleukin-1 Type I; D012795:Sialoglycoproteins