Pretreatment with granulocyte colony-stimulating factor attenuates the inflammatory response but not the bacterial load in cerebrospinal fluid duringexperimental pneumococcal meningitis in rabbits

A possible immunomodulatory role of granulocyte colony-stimulating factor ( G-CSF) was investigated in an experimental pneumococcal meningitis model in rabbits. Animals were pretreated with G-CSF (10 mu g/kg subcutaneously mic e a day) starting 48 h before in vivo and ex vivo experiments, causing a fi ve- to six-fold increase in the peripheral leukocyte level. Meningitis was induced by intracisternal inoculation of similar to 4 x 10(5) CFU of Strept ococcus pneumoniae type 3. Neutrophil pleocytosis and interleukin-8 (IL-8) levels were significantly attenuated in G-CSF-pretreated animals compared t o untreated animals (P < 0.05). Furthermore, G-CSF pretreatment significant ly delayed alterations in cerebrospinal fluid (CSF) tumor necrosis factor a lpha and IL-1 beta levels, as web as protein and glucose levels (P < 0.05). No difference in CSF bacterial concentrations was found, whereas the blood bacterial concentration was significantly decreased in G-CSF-pretreated an imals (P < 0.05). Ex vivo chemotaxis of neutrophils isolated from G-CSF-pre treated animals was significantly decreased compared to that of neutrophils from untreated animals (P < 0.05). In conclusion, G-CSF pretreatment atten uates meningeal inflammation and enhances systemic bacterial killing. Furth er preclinical studies are required to investigate whether this may affect the clinical course of meningitis and thus whether G-CSF treatment may have a beneficial role in pneumococcal meningitis.