Activation of neutrophils and inhibition of the proinflammatory cytokine response by endogenous granulocyte colony-stimulating factor in murine pneumococcal pneumonia.
Granulocyte colony-stimulating factor (G-CSF) is considered to improve host defense during infection, via increased recruitment of and enhanced performance of neutrophils and subsequent inhibition of potentially harmful proinflammatory mediators. The present study sought to determine the role of endogenous G-CSF in host defense against pneumococcal pneumonia. Patients with unilateral community-acquired pneumonia demonstrated elevated concentrations of G-CSF in bronchoalveolar lavage fluid obtained from the infected, but not from the contralateral, site. Treatment of mice with pneumococcal pneumonia with an anti-G-CSF antibody reduced neutrophil counts in lung tissue and diminished CD11b expression on pulmonary neutrophils but increased the lung concentrations of tumor necrosis factor- alpha, interleukin-1 beta, and cytokine-induced neutrophil chemoattractant. Treatment with anti-G-CSF did not influence the outgrowth of pneumococci in lungs, the dissemination of the infection, or survival in murine pneumonia. During pneumococcal pneumonia, G-CSF is produced locally at the site of the infection, where it exerts both pro- and anti-inflammatory effects.
Knapp
Sylvia
S
Laboratory of Experimental Internal Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. s.knapp@amc.uva.nl.
Hareng
Lars
L
Rijneveld
Anita W
AW
Bresser
Paul
P
van der Zee
Jaring S
JS
Florquin
Sandrine
S
Hartung
Thomas
T
van der Poll
Tom
T
D000328:Adult; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology / Q000382:microbiology; D039481:CD11b Antigen / Q000276:immunology; D002452:Cell Count; D015169:Colony Count, Microbial; D017714:Community-Acquired Infections / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D016207:Cytokines / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000276:immunology*; D006801:Humans; D008168:Lung / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018375:Neutrophil Activation / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology / Q000382:microbiology; D009195:Peroxidase / Q000276:immunology; D011018:Pneumonia, Pneumococcal / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D013296:Streptococcus pneumoniae / Q000276:immunology*
D039481:CD11b Antigen; D016207:Cytokines; D016179:Granulocyte Colony-Stimulating Factor; D009195:Peroxidase