The polysaccharide fucoidin inhibits the antibiotic-induced inflammatory cascade in experimental pneumococcal meningitis.
There is evidence that the treatment of bacterial meningitis with antibiotics liberates harmful bacterial products in the subarachnoid space (SAS). This enhances meningeal inflammation and in particular the recruitment of leukocytes into the cerebrospinal fluid (CSF), which has been shown to be more harmful than beneficial in this disease. In this study, we used a rabbit meningitis model based on intracisternal injection of live Streptococcus pneumoniae. Ampicillin (40 mg/kg of body weight given intravenously [i.v.] 16 h after induction of meningitis) caused a fivefold increase in CSF leukocytes over a 4-h period. Inhibition of leukocyte rolling by treatment with the polysaccharide fucoidin (10 mg/kg, i.v.) prevented the enhanced leukocyte extravasation into the SAS and attenuated the leakage of plasma proteins over the blood-brain barrier. These results suggest that certain polysaccharides that block leukocyte rolling have the potential to reduce leukocyte-dependent central nervous system damage in bacterial meningitis.
Granert
C
C
Department of Infectious Diseases, Huddinge Hospital, Sweden.
Raud
J
J
Lindquist
L
L
D000667:Ampicillin / Q000009:adverse effects*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D002555:Cerebrospinal Fluid / Q000737:chemistry / Q000166:cytology; D002556:Cerebrospinal Fluid Proteins / Q000032:analysis; D005260:Female; D005947:Glucose / Q000134:cerebrospinal fluid; D019344:Lactic Acid / Q000134:cerebrospinal fluid; D007958:Leukocyte Count / Q000187:drug effects; D008586:Meningitis, Pneumococcal / Q000188:drug therapy*; D010406:Penicillins / Q000009:adverse effects; D011134:Polysaccharides / Q000627:therapeutic use*; D011817:Rabbits
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002556:Cerebrospinal Fluid Proteins; D010406:Penicillins; D011134:Polysaccharides; D019344:Lactic Acid; D000667:Ampicillin; C007789:fucoidan; D005947:Glucose