Critical influence of timing of administration of granulocyte colony-stimulating factor on antibacterial effect in experimental endocarditis due to Pseudomonas aeruginosa.
The effect of human recombinant granulocyte colony-stimulating factor (hrG-CSF) in rabbits with aortic endocarditis due to Pseudomonas aeruginosa was investigated. hrG-CSF significantly increased the number of polymorphonuclear neutrophils in blood and in cardiac vegetations and the expression of the adhesin molecule CD11b on the surface of polymorphonuclear neutrophils compared with those of animals that had not received hrG-CSF. When treatment was started 72 h after bacterial challenge, hrG-CSF alone had no antibacterial effect and did not enhance the efficacy of ciprofloxacin when used in combination, even with the higher dosing regimen used (50 micrograms/kg of body weight subcutaneously every 12 h for 4 days), in terms of number of positive blood cultures, bacterial counts in vegetations, and survival. In contrast, when treatment was started 30 min prior to bacterial challenge, hrG-CSF (50 micrograms/kg injected every 12 h) decreased bacterial titers in vegetations 72 h later (6.5 +/- 0.9 versus 7.9 +/- 0.9 log10 CFU/g of vegetation for hrG-CSF and controls, respectively; P = prophylactic administration of hrG-CSF did not increase the antibacterial effect of ciprofloxacin. We concluded that the antibacterial effect of hrG-CSF in experimental endocarditis was related to the timing of its administration since hrG-CSF demonstrated a significant but transient antimicrobial effect only when treatment was initiated before bacterial challenge.
Vignes
S
S
Unité 13, Institut National de la Santé et de la Recherche Médicale, Paris, France.
Fantin
B
B
Elbim
C
C
Walker
F
F
Gougerot-Pocidalo
M A
MA
Carbon
C
C
D000818:Animals; D001011:Aorta / Q000473:pathology; D018845:CD11 Antigens / Q000032:analysis; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000648:ultrastructure; D004697:Endocarditis, Bacterial / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000627:therapeutic use*; D006410:Hematopoiesis / Q000187:drug effects; D006801:Humans; D007958:Leukocyte Count; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000382:microbiology; D011817:Rabbits; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D013997:Time Factors
D018845:CD11 Antigens; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor