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.
Akiyama
Y
Y
Growth Factor Division, National Cancer Center Research Institute, Tokyo.
Kajimura
N
N
Matsuzaki
J
J
Kikuchi
Y
Y
Imai
N
N
Tanigawa
M
M
Yamaguchi
K
K
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001806:Blood Urea Nitrogen; D001835:Body Weight / Q000187:drug effects; D001853:Bone Marrow / Q000187:drug effects*; D001854:Bone Marrow Cells; D002097:C-Reactive Protein / Q000378:metabolism; D002100:Cachexia; D002784:Cholesterol / Q000097:blood; D003001:Cloning, Molecular; D004906:Erythrocyte Count / Q000187:drug effects*; D004926:Escherichia coli; D005260:Female; D006131:Growth Inhibitors / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D015850:Interleukin-6; D007770:L-Lactate Dehydrogenase / Q000097:blood; D053605:Leukemia Inhibitory Factor; D007958:Leukocyte Count / Q000187:drug effects*; D008222:Lymphokines / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D008252:Macaca fascicularis; D008533:Megakaryocytes / Q000166:cytology / Q000187:drug effects; D051379:Mice; D008819:Mice, Nude; D009929:Organ Size / Q000187:drug effects; D010976:Platelet Count / Q000187:drug effects*; D011994:Recombinant Proteins / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D013922:Thrombocytosis; D013997:Time Factors; D014280:Triglycerides / Q000097:blood
D006131:Growth Inhibitors; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D008222:Lymphokines; D011994:Recombinant Proteins; D014280:Triglycerides; D002097:C-Reactive Protein; D002784:Cholesterol; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase