title: Haemophilus influenzae and Streptococcus pneumoniae induce different intracerebral mRNA cytokine patterns during the course of experimental bacterial meningitis.
abstract: Using in situ hybridization with radiolabelled oligonucleotide probes, we studied the mRNA expression of IL-1beta, IL-4, IL-6, IL-10, IL-12, tumour necrosis factor-alpha (TNF-alpha), TNF-beta, interferon-gamma (IFN-gamma), and transforming growth factor-beta (TGF-beta) in the brain during the lethal course of experimental meningitis in a rat model inoculated intracisternally with Haemophilus influenzae type b (Hib) or Streptococcus pneumoniae and in uninfected control rats inoculated with the same volume of PBS. The production of IL-1beta, IL-4, IL-6 and IFN-gamma was also evaluated by immunohistochemistry. In the brain of Hib-inoculated rats, there was marked mRNA expression of IL-1beta, IL-6, TNF-alpha, IL-12 and IFN-gamma. IL-1beta, IL-6 and TNF-alpha were up-regulated throughout the observation period at 2, 8 and 18 h post-inoculation (p.i.), with similar patterns of induction. The Th1 cytokines IFN-gamma and TNF-beta were up-regulated within 8 h p.i. IL-10 and TGF-beta were down-regulated at 18 h p.i., while IL-4 was not detected. In contrast, the brain of S. pneumoniae-inoculated rats showed lower levels of IL-1beta, IL-6 and TNF-alpha, but higher levels of TNF-beta and detectable mRNA expression of IL-4 when compared with Hib-inoculated rats. IL-12, IFN-gamma, IL-10 and TGF-beta exhibited similar patterns of induction in the brains of Hib- and S. pneumoniae-inoculated rats. At 18 h p.i., immunohistochemistry showed similar patterns of IL-1beta, IL-4, IL-6 and IFN-gamma as mRNA expression in the brains of Hib- and S. pneumoniae-inoculated rats. The differences of cytokine profiles induced by the two bacterial strains may imply that different immunomodulating approaches should be considered, depending on etiology.
authors.affiliation: Division of Neurology, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Diab
authors.forename: J
authors.initials: J
authors.lastname: Zhu
authors.forename: L
authors.initials: L
authors.lastname: Lindquist
authors.forename: B
authors.initials: B
authors.lastname: Wretlind
authors.forename: M
authors.initials: M
authors.lastname: Bakhiet
authors.forename: H
authors.initials: H
authors.lastname: Link
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D015342:DNA Probes; D006193:Haemophilus influenzae / Q000502:physiology*; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D008297:Male; D008583:Meningitis, Haemophilus / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008586:Meningitis, Pneumococcal / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013296:Streptococcus pneumoniae / Q000502:physiology*; D015854:Up-Regulation
chemical_list: D016207:Cytokines; D015342:DNA Probes; D012333:RNA, Messenger