Pretreatment with granulocyte colony-stimulating factor attenuates the inflammatory response but not the bacterial load in cerebrospinal fluid during experimental 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 micrograms/kg subcutaneously twice a day) starting 48 h before in vivo and ex vivo experiments, causing a five- to six-fold increase in the peripheral leukocyte level. Meningitis was induced by intracisternal inoculation of approximately 4 x 10(5) CFU of Streptococcus pneumoniae type 3. Neutrophil pleocytosis and interleukin-8 (IL-8) levels were significantly attenuated in G-CSF-pretreated animals compared to untreated animals (P < 0.05). Furthermore, G-CSF pretreatment significantly delayed alterations in cerebrospinal fluid (CSF) tumor necrosis factor alpha and IL-1beta levels, as well 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 animals (P < 0.05). Ex vivo chemotaxis of neutrophils isolated from G-CSF-pretreated animals was significantly decreased compared to that of neutrophils from untreated animals (P < 0.05). In conclusion, G-CSF pretreatment attenuates meningeal inflammation and enhances systemic bacterial killing. Further 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.
Ostergaard
C
C
Division of Microbiology, Department of Research and Development, Statens Serum Institut, Copenhagen, Denmark. coa@ssi.dk
Benfield
T
T
Gesser
B
B
Kharazmi
A
A
Frimodt-Møller
N
N
Espersen
F
F
Lundgren
J D
JD
D000818:Animals; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology* / Q000382:microbiology; D007279:Injections, Subcutaneous; D008586:Meningitis, Pneumococcal / Q000134:cerebrospinal fluid / Q000188:drug therapy / Q000276:immunology* / Q000382:microbiology; D011817:Rabbits; D013296:Streptococcus pneumoniae / Q000302:isolation & purification*
D016179:Granulocyte Colony-Stimulating Factor