Protective effect of SPR-901 (RBS) on the decrease of peripheral leukocyte number in 5-fluorouracil-treated mice.
5-Fluorouracil (5-FU) induces a decrease in the number of peripheral leukocytes (leukopenia), which is one of the major obstacles in the chemotherapy of cancer. The number of peripheral leukocytes decreased by day 4 in mice injected i.p. with 130 mg/kg of 5-FU and recovered to the normal level by day 8. Such a decrease by 5-FU was prevented to some extent by the oral administration of 30 mg/kg/day of SPR-901. Proliferative responses of bone marrow cells to granulocyte/macrophage colony stimulating factor (GM-CSF) or granulocyte colony stimulating factor (G-CSF) were suppressed by 5-FU treatment and their recoveries were enhanced by SPR-901. The serum level of IL-6 in 5-FU-treated mice was increased by SPR-901. All of the mice treated with 300 mg/kg of 5-FU in combination with SPR-901 survived over 15 days, however, only 4 of 10 mice treated only with 300 mg/kg of 5-FU survived. These results suggest that SPR-901 acts on macrophages directly or indirectly, giving rise to the enhanced production of IL-1, IL-6, and other factors. Some of the factors derived from SPR-901 activated macrophages, perhaps mainly IL-6, act on the early stage of development of multipotent bone marrow progenitors synergistically with GM-CSF.
Miyazaki
H
H
Department of Immunology, Kyushu University, Fukuoka, Japan.
Yoshikai
Y
Y
Tanaka
M
M
Takeda
Y
Y
Takeo
S
S
Nomoto
K
K
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D016207:Cytokines / Q000032:analysis; D005260:Female; D005472:Fluorouracil / Q000633:toxicity*; D005936:Glucans / Q000494:pharmacology*; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D007958:Leukocyte Count / Q000187:drug effects; D007970:Leukopenia / Q000139:chemically induced / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C
D000970:Antineoplastic Agents; D016207:Cytokines; D005936:Glucans; D015850:Interleukin-6; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D005472:Fluorouracil