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In pneumococcal meningitis inflammatory mediators such as tumor necrosis factor alpha (TNF
α) are produced in large quantities and play a major role in pathogenesis. It is not known exactly which cells produce these mediators during infection. We investigated the localisation of TNF
α-mRNA in the central nervous system (CNS) by in situ hybridisation during experimental
Streptococcus pneumoniae meningitis. TNF-positive cells were detected only in inflammatory infiltrates within the meninges. Cells within the brain parenchyma and the choroid plexus were completely negative. After monocyte depletion, no TNF
α-mRNA positive cells were detected in the CNS. These findings suggest that TNF
α in pneumococcal meningitis is produced in the CNS mainly by blood-derived, infiltrating monocytes.