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Infection and Immunity, July 1999, p. 3430-3436, Vol. 67, No. 7
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Pretreatment with Granulocyte Colony-Stimulating Factor Attenuates the Inflammatory Response but Not the Bacterial Load in Cerebrospinal Fluid during Experimental Pneumococcal Meningitis in Rabbits

Christian Østergaard,1,* Thomas Benfield,2 Borbola Gesser,3 Arsalan Kharazmi,4 Niels Frimodt-Møller,1 Frank Espersen,1 and Jens D. Lundgren2

Division of Microbiology, Department of Research and Development, Statens Serum Institut,1 Department of Infectious Diseases, University Hospital (Hvidovre Hospital),2 and Department of Clinical Microbiology, University Hospital (Rigshospitalet),4 Copenhagen, and Department of Dermatology, University Hospital (Marselisborg Hospital), Århus,3 Denmark

Received 30 November 1998/Returned for modification 5 March 1999/Accepted 13 April 1999

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 µg/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 ~4 × 105 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.

* Corresponding author. Mailing address: Division of Microbiology, Department of Research and Development, Statens Serum Institut, 5 Artillerivej, DK-2300 Copenhagen S, Denmark. Phone: 45 32688208. Fax: 45 32683887. E-mail: coa{at}ssi.dk.

Infection and Immunity, July 1999, p. 3430-3436, Vol. 67, No. 7
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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