Recombinant murine granulocyte colony-stimulating factor protects against acute disseminated Candida albicans infection in nonneutropenic mice.
The effect of recombinant granulocyte colony-stimulating factor (rG-CSF) on acute disseminated Candida albicans infection in nonneutropenic mice was investigated. Mice treated with a single dose of rG-CSF showed a significantly reduced mortality (28% vs. 90%; P < .001). The outgrowth of C. albicans from the kidneys, spleens, and livers of rG-CSF-treated mice was significantly reduced (log cfu/g of kidney, 5.54 vs. 7.13; P < .001), as were circulating tumor necrosis factor-alpha and interleukin-1beta. After rG-CSF, the kidneys showed fewer infectious infiltrates, enhanced granulocyte influx, and almost complete absence of hyphal outgrowth. During peritoneal C. albicans infection, rG-CSF enhanced influx of granulocytes to the site of infection, and exudate granulocytes showed increased oxygen radical production. These results indicate that rG-CSF enhances host resistance to disseminated candidiasis in nonneutropenic mice through activation of granulocytes and their recruitment to the site of infection.
Kullberg
B J
BJ
Department of Medicine, Catholic University Nijmegen and University Hospital, The Netherlands. B.Kullberg@aig.azn.nl
Netea
M G
MG
Curfs
J H
JH
Keuter
M
M
Meis
J F
JF
van der Meer
J W
JW
D000818:Animals; D002177:Candidiasis / Q000188:drug therapy*; D018450:Disease Progression; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000627:therapeutic use*; D006098:Granulocytes / Q000276:immunology; D007375:Interleukin-1 / Q000378:metabolism; D007668:Kidney / Q000382:microbiology; D008099:Liver / Q000382:microbiology; D051379:Mice; D008808:Mice, Inbred CBA; D010537:Peritoneum / Q000276:immunology / Q000382:microbiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000382:microbiology; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism
D007375:Interleukin-1; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D016179:Granulocyte Colony-Stimulating Factor