Haemophilus influenzae and Streptococcus pneumoniae induce different intracerebral mRNA cytokine patterns during the course of experimental bacterial meningitis.
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.
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Division of Neurology, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden.
Zhu
J
J
Lindquist
L
L
Wretlind
B
B
Bakhiet
M
M
Link
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H
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
D016207:Cytokines; D015342:DNA Probes; D012333:RNA, Messenger