Cytokine mRNA Profiles during the Course of Experimental Haemophilus influenzaeBacterial Meningitis

Abstract

Intraperitoneal inoculation of Haemophilus influenzaetype b (Hib) to 3-week-old Sprague–Dawley rats resulted in nonlethal meningitis with high levels of leukocytes in the cerebrospinal fluid (CSF) and positive bacterial culture. Using in situhybridization, levels of cytokine mRNA-expressing cells were determined in the brain, CSF, and spleen from Hib-inoculated and uninfected control rats. IFN-γ, IL-1β, IL-4, IL-6, IL-10, IL-12, and TNF-α mRNA levels were elevated at 12 hr postinoculation (pi) in spleen and CSF. At this time point, strong expression of IL-6 and TGF-β was detected in the brain, and also of IL-10 at 48 hr while IFN-γ and IL-12 were expressed at very low levels throughout the observation time. Delayed cytokine induction occurred in CSF compared to spleen and brain. TGF-β was high in CSF at 48 hr, and some elevation of IL-1β, IL-6, IL-10, TNF-α, IFN-γ, and IL-12 was evident at 72 hr pi. This may suggest measures that promote production of TGF-β and/or IL-10 should be evaluated in treatment of bacterial meningitis.