In vivo effect of recombinant human leukemia inhibitory factor in primates

Leukemia inhibitory factor (LIF) is known to be a causative factor for cachexia and thrombocytosis in nude mice bearing human cancer cells. In the present study, we investigated whether recombinant human (rh) LIF can induce these biological activities in a primate model. rhLIF was synthesized by the expression of LIF protein in Escherichia coli. rhLIF (5, 20, or 80 micrograms/kg) was administered subcutaneously twice daily to cynomolgus monkeys for 14 consecutive days. A remarkable decrease of body weight (10%) was observed in the 80 micrograms/kg/day group. Approximately two-fold increases in platelet counts were observed at doses higher than 5 micrograms/kg/day when compared with control counts. These biological effects disappeared soon after the cessation of rhLIF treatment. Macroscopically, a remarkable reduction in subcutaneous fatty tissues and severe splenomegaly were observed. The results of this study demonstrate that rhLIF induces weight loss and thrombocytosis in a primate model.