Protective effect of recombinant human leukemia inhibitory factor against thrombocytopenia in carboplatin-treated mice.
The protective effect of recombinant human leukemia inhibitory factor (rhLIF) against development of thrombocytopenia in carboplatin (CBDCA; cis-diammine-1,1-cyclobutane dicarboxylate platinum II)-treated mice was examined. The optimal dose of rhLIF was determined by administering doses of rhLIF ranging from 0.2 to 20 micrograms/day intraperitoneally to normal BALB/c mice, and by analyzing platelet counts. Platelet counts significantly increased at doses over 0.2 microgram/day. When 20 micrograms/day rhLIF was injected for 7 days, platelet counts increased to 240% of control. A remarkable weight loss occurred in the 20 micrograms/day group, but no weight loss was detected at doses of less than 10 micrograms/day. The rhLIF dose of 4 micrograms/day was therefore used to examine the protective effect against carboplatin-induced thrombocytopenia in mice. The intravenous injection of 100 mg/kg carboplatin caused a significant thrombocytopenia with a nadir on day 8. The administration of 4 micrograms/day rhLIF intraperitoneally for 7 days promoted the recovery of platelet counts from day 5 after the injection of carboplatin. These results suggest that rhLIF at a suboptimal dose might be a useful therapeutic agent for chemotherapy-induced thrombocytopenia.
Akiyama
Y
Y
Growth Factor Division, National Cancer Center Research Institute, Tokyo.
Kikuchi
Y
Y
Matsuzaki
J
J
Kajimura
N
N
Ohue
C
C
Yamaguchi
K
K
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D016190:Carboplatin / Q000633:toxicity*; D003114:Colony-Forming Units Assay; D006131:Growth Inhibitors / Q000097:blood / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000097:blood / Q000494:pharmacology*; D008297:Male; D008533:Megakaryocytes / Q000166:cytology* / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000097:blood / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D013921:Thrombocytopenia / Q000139:chemically induced / Q000517:prevention & control*; D013997:Time Factors
D006131:Growth Inhibitors; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D008222:Lymphokines; D011994:Recombinant Proteins; D016190:Carboplatin