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) L IF earn induce these biological activities in a primate model. rhLIF w as synthesized by the expression of LIF protein in Escherichia coli. r hLIF (5, 20, or 80 mu g/kg) was administered subcutaneously twice dail y to cynomolgus monkeys for 14 consecutive days. A remarkable decrease of body weight (10%) was observed in the 80 mu g/kg/day group, Approx imately two-fold increases in platelet counts were observed at doses h igher than 5 mu g/kg/day when compared with control counts, These biol ogical effects disappeared soon after the cessation of rhLIF treatment . Macroscopically, a remarkable reduction in subcutaneous fatty tissue s and severe splenomegaly were observed, The results of this study dem onstrate that rhLIF induces weight loss and thrombocytosis in a primat e model.