Brain parenchymal TNF-α and IL-1β induction in experimental pneumococcal meningitis

• We examined triggers of brain inflammation in murine pneumococcal meningitis.
• TNF-α and IL-1β were assessed by real time PCR and in situ hybridization.
• Brain cytokine upregulation was independent of cerebrospinal fluid leukocytosis.
• Brain cytokine upregulation was independent of pneumococcal toxins.
• Pneumococcal cell wall triggered brain TNF-α and IL-1β mRNA induction.

Triggers of brain inflammation in pneumococcal meningitis are unknown. TNF-α and IL-1β were upregulated (real time PCR and in situ hybridization) in neurons and astrocytes time-dependently and maximally in the hippocampus during murine pneumococcal meningitis. Upregulation of TNF-α and IL-1β mRNA in the brain parenchyma was independent of cerebrospinal fluid leukocytosis, pneumococcal pneumolysin and H2O2, but it was potently induced by pneumococcal cell wall (PCW) fragments. Brain TNF-α mRNA was downregulated by a matrix metalloproteinases inhibitor. PCW fragments were located in the brain parenchyma. In conclusion, PCW fragments and matrix metalloproteinases trigger cytokine induction in the brain parenchyma during pneumococcal meningitis.