TY - JOUR
T1 - Interleukin-18 gene-deficient mice show enhanced defense and reduced inflammation during pneumococcal meningitis
AU - Zwijnenburg, Petra J G
AU - van der Poll, Tom
AU - Florquin, Sandrine
AU - Akira, Shizuo
AU - Takeda, Kiyoshi
AU - Roord, John J
AU - van Furth, A Marceline
PY - 2003/5
Y1 - 2003/5
N2 - 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.
AB - 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.
KW - Adjuvants, Immunologic/biosynthesis
KW - Animals
KW - Brain/pathology
KW - Cell Movement/genetics
KW - Cerebrospinal Fluid/cytology
KW - Chemokines/secretion
KW - Colony Count, Microbial
KW - Cytokines/secretion
KW - Down-Regulation/genetics
KW - Immunity, Innate/genetics
KW - Interleukin-18/biosynthesis
KW - Leukocytes/pathology
KW - Meningitis, Pneumococcal/genetics
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - Streptococcus pneumoniae/growth & development
KW - Survival Rate
KW - Up-Regulation/genetics
M3 - Article
C2 - 12742650
VL - 138
SP - 31
EP - 37
JO - Journal of Neuroimmunology
JF - Journal of Neuroimmunology
SN - 0165-5728
IS - 1-2
ER -