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Leukocyte infiltration of the CSF and brain parenchyma and other parameters of inflammation during pneumococcal meningitis were investigated after reduction of meningeal macrophages in rabbits by intracisternal injection of dichloromethylene-diphosphonate (Cl2MDP)-containing liposomes. Macrophages in the meninges were reduced, in median, by approximately 77% after three intrathecal injections of 100 microl of liposomes containing Cl2MDP at 12 h intervals. Production of the cytokines interleukin-1 and tumor necrosis factor-alpha as well as infiltration of the CSF and nervous tissue by leukocytes was not significantly altered in infected animals after treatment with Cl2MDP-containing liposomes. The median CSF concentration of neuron specific enolase (NSE) as a parameter of neuronal damage was higher in infected Cl2MDP-treated animals (median [median (25th/75th percentiles): 44.7 (33.2/54.3) microg/l vs. 13.9 (10.4/23.9) microg/l; P = 0.01]). Therefore, the reduction of meningeal macrophages does not appear to attenuate inflammation in the subarachnoid space in experimental pneumococcal meningitis. Meningeal macrophages seem, however, to be important for the protection of neuronal tissue in bacterial meningitis.