Interleukin-18 gene-deficient mice show enhanced defense and reduced inflammation during pneumococcal meningitis.
To determine the role of endogenous interleukin-18 (IL-18) in pneumococcal meningitis, meningitis was induced in IL-18 gene-deficient (IL-18(-/-)) and wild-type (WT) mice by intranasal inoculation of Streptococcus pneumoniae with hyaluronidase. Induction of meningitis resulted in an upregulation of both pro- and mature IL-18 in brain tissue in WT mice. IL-18(-/-) and WT mice were equally susceptible to develop meningitis after intranasal infection, yet IL-18(-/-) mice showed a prolonged survival and a suppressed inflammatory response, as reflected by a less profound inflammatory infiltrate around the meninges and lower concentrations of cytokines and chemokines in brain tissue. These findings suggest that endogenous IL-18 contributes to a detrimental inflammatory response during pneumococcal meningitis and that elimination of IL-18 may improve the outcome of this disease.
Zwijnenburg
Petra J G
PJ
Department of Pediatrics, Vrije Universiteit Medical Center, de Boelelaan 1117, 1081 HV Amsterdam, The Netherlands. p.j.zwijnenburg@amc.uva.nl
van der Poll
Tom
T
Florquin
Sandrine
S
Akira
Shizuo
S
Takeda
Kiyoshi
K
Roord
John J
JJ
van Furth
A Marceline
AM
D000276:Adjuvants, Immunologic / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D000818:Animals; D001921:Brain / Q000473:pathology; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D002555:Cerebrospinal Fluid / Q000166:cytology; D018925:Chemokines / Q000378:metabolism; D015169:Colony Count, Microbial; D016207:Cytokines / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology*; D007113:Immunity, Innate / Q000235:genetics; D020382:Interleukin-18 / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D007962:Leukocytes / Q000473:pathology; D008586:Meningitis, Pneumococcal / Q000235:genetics* / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013296:Streptococcus pneumoniae / Q000254:growth & development / Q000276:immunology; D015996:Survival Rate; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology*
D000276:Adjuvants, Immunologic; D018925:Chemokines; D016207:Cytokines; D020382:Interleukin-18