Therapeutic efficacy of granulocyte colony-stimulating factor alone and in combination with antibiotics against Pseudomonas aeruginosa infections in mice

Abstract

The therapeutic efficacy of granulocyte colony-stimulating factor (G-CSF) against an experimental intramuscular infection induced by Pseudomonas aeruginosa in mice was confirmed. Bacterial growth in the infected thigh muscle was suppressed by G-CSF treatment. The change in the number of peripheral blood polymorphonuclear leukocytes (PMN) after bacterial challenge was investigated. The results showed that G-CSF could stimulate stronger defense mechanisms after stimulation by bacterial challenge. In the G-CSF-treated group, more clusters of matured PMN were observed in the infected thigh muscle 6 h after bacterial challenge. Next, the correlation between the number of PMN in the blood at the time of infection and the therapeutic efficacy of antibiotics was investigated. The therapeutic efficacy of ceftazidime, a P-lactam antibiotic, was affected by the number of blood PMN at the time of infection. In particular, a decrease of peripheral blood PMN at the time of infection resulted in a dramatic decrease in the efficacy of ceftazidime. The reduction in leukopenia by G-CSF remarkably strengthened the therapeutic effect of antibiotics in mice.

Granulocyte colony‐stimulating factor enhances protection by anti‐K1 capsular IgM antibody in murine Escherichia coli sepsis

“…Our results, obtained in a prophylaxis model, as well as the favourable results reported by others in therapeutic intervention models [15,16], justify further studies on the role of G-CSF treatment in non-neutropenic infections. Of interest, a recent paper reported protection in a rat pneumococcal pneumonia model following therapeutic but not prophylactic administration of human G-CSF [17].…”

Augmentation of Host Resistance against Bacterial Infection by Treatment with Leustroducsin B, a New CSF Inducer

“…In this report, we showed that LSN B, a new CSF inducer derived from S. platensis, has a strong activity in protecting hosts against infection with E. coli. At first, we expected that LSN B induced G-or GM-CSF in vivo and thereby enhanced host resistance by stimulating bactericidal activity of neutrophils because these cytokines are reported to enhance the host resistance against several infections (2,(14)(15)(16)(17)22). However, we could not detect the induction of GM-CSF in vivo.…”

“…G-CSF and GM-CSF are reported to enhance resistance against several infections in normal and immunosuppressed hosts in experimental models (2,(14)(15)(16)(17)22). These cytokines also enhance the Fig.…”

Effects of Adjunctive Treatment with Combined Cytokines in a Neutropenic Mouse Model of Multidrug‐Resistant Enterococcus faecalis Septicemia

“…15,16,20 The main finding was that a combination of G-CSF and IFN-␥ as an adjunct to vancomycin resulted in no improvement in antienterococcal treatment outcome compared with adjunctive therapy with only G-CSF. Although copious literature describes the beneficial effect of G-CSF or IFN-␥ in enhancing antibiotic therapy in animal infection models as well as in humans, [24][25][26][27][28][29] information regarding an adjunctive combination of cytokines in treating infections is sparse. Given reports of combination G-CSF-and IFN-␥induced additive in vitro antimicrobial activity, 30,31 it was reasoned that it is possible that such an interaction may be seen against enterococci.…”