title: Brain parenchymal TNF-α and IL-1β induction in experimental pneumococcal meningitis.
abstract: Triggers of brain inflammation in pneumococcal meningitis are unknown. TNF-α and IL-1β were upregulated (real time PCR and in situ hybridization) in neurons and astrocytes time-dependently and maximally in the hippocampus during murine pneumococcal meningitis. Upregulation of TNF-α and IL-1β mRNA in the brain parenchyma was independent of cerebrospinal fluid leukocytosis, pneumococcal pneumolysin and H2O2, but it was potently induced by pneumococcal cell wall (PCW) fragments. Brain TNF-α mRNA was downregulated by a matrix metalloproteinases inhibitor. PCW fragments were located in the brain parenchyma. In conclusion, PCW fragments and matrix metalloproteinases trigger cytokine induction in the brain parenchyma during pneumococcal meningitis.
authors.affiliation: Department of Neurology, Charité Universitätsmedizin Berlin, Germany; Department of Orthopedics and Traumatology, University Freiburg, Germany.
authors.forename: Kaywan
authors.initials: K
authors.lastname: Izadpanah
authors.affiliation: Department of Neurology, Charité Universitätsmedizin Berlin, Germany.
authors.forename: Dorette
authors.initials: D
authors.lastname: Freyer
authors.affiliation: Department of Neurology, Charité Universitätsmedizin Berlin, Germany; Department of Neurology, Klinikum Klagenfurt, Austria.
authors.forename: Joerg R
authors.initials: JR
authors.lastname: Weber
authors.affiliation: Department of Neurology, Charité Universitätsmedizin Berlin, Germany; Department of Internal Medicine, Division Neurology, College of Medicine and Health Sciences, United Arab Emirates University, United Arab Emirates. Electronic address: johann.braun@charite.de.
authors.forename: Johann S
authors.initials: JS
authors.lastname: Braun
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology / Q000627:therapeutic use; D001921:Brain / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology*; D018821:CD18 Antigens / Q000276:immunology; D015169:Colony Count, Microbial; D004151:Dipeptides / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D004388:Dura Mater / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism*; D008297:Male; D061965:Matrix Metalloproteinase Inhibitors / Q000627:therapeutic use; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008586:Meningitis, Pneumococcal / Q000188:drug therapy / Q000209:etiology / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010767:Phosphorylcholine / Q000378:metabolism; D013296:Streptococcus pneumoniae / Q000472:pathogenicity; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
chemical_list: D000906:Antibodies; D018821:CD18 Antigens; D004151:Dipeptides; D005904:Glial Fibrillary Acidic Protein; D053583:Interleukin-1beta; D061965:Matrix Metalloproteinase Inhibitors; C078131:N-(2(R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl)-L-tryptophan methylamide; D014409:Tumor Necrosis Factor-alpha; D010767:Phosphorylcholine; D020782:Matrix Metalloproteinases
keywords: Brain; IL-1β; Meningitis; Pneumococcal cell wall; S. pneumoniae; TNF-α