Elimination of blood-derived macrophages inhibits the release of interleukin-1 and the entry of leukocytes into the cerebrospinal fluid in experimental pneumococcal meningitis.

Parameters of inflammation during pneumococcal meningitis were determined in rabbits after monocyte elimination by dichloromethylene diphosphonate (Cl(2)MDP)-containing mannosylated liposomes in comparison with untreated controls. Monocyte depletion reduced the migration of white blood cells into the cerebrospinal fluid (CSF) (medians: 42 versus 2146/mm3 at 18 h, 323 versus 7413/mm3 at 24 h p.i., p < 0.01). CSF IL-1beta concentrations were lower in depleted animals (379 versus 3282 pg/ml, 24 h p.i., p < 0.01), whereas TNF-alpha concentrations were not different. Monocyte-depleted animals lost body temperature during the experiment carried out in anaesthesia (p = 0.01) indicating that macrophages are necessary for thermogenesis during meningitis.