Mechanism of protective effect of recombinant human granulocyte colony-stimulating factor (rG-CSF) on Pseudomonas...

Decrease in resistance to systemic Pseudomonas infection in cyclophosphamide (CPA)-induced neutropenic mice was prevented by injections of recombinant human granulocyte colony-stimulating factor (rG-CSF). In order to explore mechanism of the prevention of CPA-induced decrease in the anti-infectious resistance by rG-CSF, CPA-treated and then rG-CSF-injected mice were inoculated i.p. with P. aeruginosa, and growth of the infecting bacteria and infiltration of leukocytes in the peritoneal cavity were determined. In the mice who had received 4 daily s.c. injections of rG-CSF from the day after CPA-injection, a large number of neutrophils were mobilized into the peritoneal cavity in response to the bacterial inoculation and growth of the infecting Pseudomonas in the cavity was markedly inhibited, whereas in CPA-induced neutropenic mice few neutrophils were mobilized and the infecting bacteria proliferated vigorously in the peritoneal cavity. These results suggest that administration of rG-CSF prevents CPA-induced neutropenia and neutrophils circulating at normal level in the number are normally mobilized into the peritoneal cavity in response to Pseudomonas inoculation, and that the mobilized neutrophils inhibit proliferation of the infecting Pseudomonas.