THE POLYSACCHARIDE FUCOIDIN INHIBITS THE ANTIBIOTIC-INDUCED INFLAMMATORY CASCADE IN EXPERIMENTAL PNEUMOCOCCAL MENINGITIS

There is evidence that the treatment of bacterial meningitis with anti biotics liberates harmful bacterial products in the subarachnoid space (SAS). This enhances meningeal inflammation and in particular the rec ruitment of leukocytes into the cerebrospinal fluid (CSF), which has b een shown to be mare harmful than beneficial in this disease. In this study, we used a rabbit meningitis model based on intracisternal injec tion of live Streptococcus pneumoniae. Ampicillin (40 mg/kg of body we ight given intravenously [i.v.] 16 h after induction of meningitis) ca used a fivefold increase in CSF leukocytes over a 4-h period. Inhibiti on of leukocyte rolling by treatment with the polysaccharide fucoidin (10 mg/kg, i.v.) prevented the enhanced leukocyte extravasation into t he SAS and attenuated the leakage of plasma proteins over the blood-br ain barrier, These results suggest that certain polysaccharides that b lock leukocyte rolling have the potential to reduce leukocyte-dependen t central nervous system damage in bacterial meningitis.