[Study of the prophylactic and therapeutic effect of human granulocyte-colony stimulating factor (G-CSF) on experimental pyelonephritis induced by pseudomonas aeruginosa in neutropenic mice]

Abstract

We investigated the prophylactic and therapeutic effect of human granulocyte-colony stimulating factor (G-CSF) on mice with ascending pyelonephritis induced by Pseudomonas aeruginosa (G-group). This experimental model was established by a two course administration of cyclophosphamide, so that it kept the mice in a neutropenic status (around 2000 white blood cells/mm3) from the time of infection to the time of sacrifice. The cyclophosphamide-treated group increased their susceptibility more than the control group. In the cyclophosphamide-treated group, the prophylactic administration of G-CSF (2 micrograms/day/mouse) yielded a lower incidence of infection and of infection-induced mortality than that of saline alone. However, the therapeutic administration of G-CSF did not produce significant decreases of these rates, suggesting that this type of administration had no effect on infection. At the time of sacrifice, the prophylactic administration of G-CSF increased the number of neutrophils, while at the time of induced infection, no increase of neutrophils was found. G-CSF therapeutic administration was not able to increase neutrophils during the experiment. An investigation of the bacterial capacity of peritoneal exudate neutrophils revealed that G-CSF prophylactic administration accelerated its capacity, although cyclophosphamide alone did not. These results suggest that G-CSF has a prophylactic effect on bacterial infection in neutropenic mice, and that this effect, in part, depends upon both the increase of neutrophils and the acceleration of bactericidal capacity produced by G-CSF.