Effects of recombinant human granulocyte colony-stimulating factor on the mice receiving bone marrow transplantation following lethal irradiation: acceleration of recovery of the peripheral blood neutrophils and potentiation of anti-Pseudomonas resistance.
The effects of recombinant human granulocyte colony-stimulating factor (rG-CSF) on the recovery of peripheral blood neutrophil counts and resistance to i.p. infection by Pseudomonas aeruginosa were studied using a mouse bone marrow transplantation (BMT) model. A severe neutropenic period continued in the BMT mice for greater than 9 days following BMT. In contrast, the number of peripheral blood neutrophils in the BMT mice that received a daily administration of 2.5 micrograms of rG-CSF following BMT returned to normal by day 9. Thus, rG-CSF accelerated the recovery of the peripheral blood neutrophil counts in BMT mice. Anti-Pseudomonas resistance of the control BMT mice examined on days 7, 9, and 11 following BMT was one fifteenth to one fiftieth of normal mice, as indicated by the LD50 value. The anti-Pseudomonas resistance was elevated six- to sevenfold by the rG-CSF treatment. A marked increase in the neutrophils exudating into the peritoneal cavity in response to casein injection was observed in the rG-CSF-treated BMT mice. In addition, the reduced superoxide generative and phagocytic activity of the peritoneal neutrophils of the BMT mice were restored to normal by the rG-CSF treatment. It is suggested that rG-CSF potentiated anti-Pseudomonas resistance of the BMT mice by increasing neutrophils migrating to the infection site and restoring their functions; this may result from a prompt recovery of the peripheral blood neutrophil level together with the effect on neutrophil functions. These results indicate the clinical usefulness of rG-CSF in applications for BMT.
Tamura
M
M
Fuji-Gotemba Research Laboratories, Chugai Pharmaceutical Company, Gotemba, Japan.
Matsumoto
M
M
Yoshino
T
T
Matsubara
S
S
Imai
N
N
Ono
M
M
Yokota
T
T
D000818:Animals; D001772:Blood Cell Count / Q000187:drug effects; D016026:Bone Marrow Transplantation; D002364:Caseins / Q000494:pharmacology; D004198:Disease Susceptibility; D005122:Exudates and Transudates / Q000166:cytology / Q000378:metabolism; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D010529:Peritoneal Cavity; D011550:Pseudomonas aeruginosa / Q000276:immunology*; D011994:Recombinant Proteins; D014916:Whole-Body Irradiation
D002364:Caseins; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor