Macrophage colony-stimulating factor (M-CSF) prevents infectious death induced by chemotherapy in mice, while granulocyte-CSF does not.
To clarify the effect of granulocyte colony-stimulating factor (G-CSF) and macrophage colony-stimulating factor (M-CSF/CSF-1) on chemotherapy-induced infection, we estimated the effect of those CSFs on a mouse model under severe myelosuppression. First, we established an animal model in which 48.9% (22/45) of C3H/Hej mice died of sepsis related to severe myelosuppression after intraperitoneal administration of a single dose (9 mg/kg) of mitomycin C (MMC). G-CSF or M-CSF was administered to this model on various administration schedules after chemotherapy, and the effect of those CSFs on survival rates, peripheral blood granulocyte counts, expression of adhesion molecules (CD11a, CD11b, CD18) on granulocytes and granulocyte function (phagocytosis and superoxide anion production) were examined. In all G-CSF administration groups, peripheral blood granulocyte counts were increased, but improvements in expression of adhesion molecules such as CD11a and CD18, and granulocyte function were less marked and survival rates were not improved. Meanwhile, when M-CSF was administered from 1 to 7 days after chemotherapy, granulocyte and platelet counts were increased, and moreover, expression of adhesion molecules and granulocyte function were markedly improved. Furthermore, the survival rate was significantly improved to 77.8% (28/36) compared with the MMC group (P < 0.05). Positive rate of blood culture examination at 7 days after chemotherapy in the M group was 0%, and was significantly lower than that in the G group (40%) and the MMC group (40%) (P < 0.05). These results demonstrated that it is important not only to increase the granulocyte counts, but also to improve granulocyte functions for preventing infection under myelosuppression after chemotherapy.
Hidaka
Takao
T
Department of Obstetrics and Gynecology, Toyama Medical and Pharmaceutical University, Toyama 930-0194, Japan.
Fujimura
Masaki
M
Nakashima
Akitoshi
A
Higuma
Subaru
S
Yamagishi
Naoko
N
Tsuda
Hiroshi
H
Sakai
Masatoshi
M
Saito
Shigeru
S
D000818:Animals; D000838:Anions; D000970:Antineoplastic Agents / Q000494:pharmacology; D001792:Blood Platelets / Q000166:cytology; D040881:CD11a Antigen / Q000096:biosynthesis; D018821:CD18 Antigens / Q000096:biosynthesis; D002448:Cell Adhesion; D003141:Communicable Diseases / Q000188:drug therapy* / Q000401:mortality; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism / Q000494:pharmacology*; D006098:Granulocytes / Q000378:metabolism; D007958:Leukocyte Count; D007962:Leukocytes / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D016685:Mitomycin / Q000494:pharmacology; D010587:Phagocytosis; D018805:Sepsis / Q000401:mortality / Q000517:prevention & control*; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors
D000838:Anions; D000970:Antineoplastic Agents; D040881:CD11a Antigen; D018821:CD18 Antigens; D013481:Superoxides; D016179:Granulocyte Colony-Stimulating Factor; D016685:Mitomycin; D016173:Macrophage Colony-Stimulating Factor