CYTOKINE MESSENGER-RNA PROFILES DURING THE COURSE OF EXPERIMENTAL HAEMOPHILUS-INFLUENZAE BACTERIAL-MENINGITIS

Intraperitoneal inoculation of Haemophilus influenzae type b (Rib) to 3-week-old Sprague-Dawley rats resulted in nonlethal meningitis with h igh levels of leukocytes in the cerebrospinal fluid (CSF) and positive bacterial culture. Using in situ hybridization, levels of cytokine mR NA-expressing cells were determined in the brain, CSF, and spleen from Hib-inoculated and uninfected control rats. IFN-gamma, IL-1 beta, IL- 4, IL-6, IL-10, IL-12, and TNF-alpha mRNA levels were elevated at 12 h r postinoculation (pi) in spleen and CSF. At this time point, strong e xpression of IL-6 and TGF-beta was detected in the brain, and also of IL-10 at 48 hr while IFN-gamma and IL-12 were expressed at very low le vels throughout the observation time. Delayed cytokine induction occur red in CSF compared to spleen and brain. TGF-beta was high in CSF at 4 8 hr, and some elevation of IL-1 beta, IL-6, IL-10, TNF-alpha, IFN-gam ma, and IL-12 was evident at 72 hr pi. This may suggest measures that promote production of TGF-beta and/or IL-10 should be evaluated in tre atment of bacterial meningitis. (C) 1997 Academic Press.