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.