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Cytokine mRNA profiles during the course of experimental Haemophilus influenzae bacterial meningitis
1Division of Neurology, Karolinska Institute, Huddinge Hospital, Stockholm, Sweden.
Abstract:
Intraperitoneal inoculation of Haemophilus influenzae type 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 situ hybridization, levels of cytokine mRNA-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 hr postinoculation (pi) in spleen and CSF. At this time point, strong expression 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 levels throughout the observation time. Delayed cytokine induction occurred in CSF compared to spleen and brain. TGF-beta was high in CSF at 48 hr, and some elevation of IL-1 beta, IL-6, IL-10, TNF-alpha, IFN-gamma, 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 treatment of bacterial meningitis.
Insights
This study shows that Haemophilus influenzae type b (Hib) meningitis in rats triggers cytokine responses in the brain, spleen, and cerebrospinal fluid (CSF). Promoting TGF-beta and IL-10 may aid in treating bacterial meningitis.
Area of Science:
- Immunology
- Neuroscience
- Microbiology
Background:
- Bacterial meningitis, particularly Haemophilus influenzae type b (Hib), poses significant health risks.
- Understanding the host's immune response, including cytokine profiles, is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the temporal expression of cytokine mRNA in Sprague-Dawley rats following intraperitoneal inoculation with Hib.
- To determine the localization of cytokine-expressing cells in the brain, cerebrospinal fluid (CSF), and spleen.
Main Methods:
- Intraperitoneal inoculation of 3-week-old Sprague-Dawley rats with Hib.
- In situ hybridization to quantify cytokine mRNA levels in brain, CSF, and spleen at various time points post-inoculation (12, 48, and 72 hours).
- Monitoring for nonlethal meningitis, leukocyte counts in CSF, and bacterial cultures.
Main Results:
- Elevated levels of IFN-gamma, IL-1 beta, IL-4, IL-6, IL-10, IL-12, and TNF-alpha mRNA were observed in spleen and CSF at 12 hours post-inoculation.
- Strong expression of IL-6 and TGF-beta was detected in the brain at 12 hours, with IL-10 elevated at 48 hours.
- Delayed cytokine induction was noted in the CSF compared to spleen and brain, with TGF-beta peaking at 48 hours and other cytokines showing elevation at 72 hours.
Conclusions:
- The study reveals a dynamic cytokine response in rats with Hib-induced meningitis, with distinct temporal and spatial patterns.
- The findings suggest that therapeutic strategies aimed at enhancing TGF-beta and/or IL-10 production could be beneficial for treating bacterial meningitis.