In vivoEffect of Recombinant Human Leukemia Inhibitory Factor in Primates

Abstract

Leukemia inhibitory factor(LIF) is known to be a causative factor for cacbexia 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 80μ/kg) was administered subcutaneously twice daily to cynomolgus monkeys for 14 consecutive days. A remarkable decrease of body weight (10%) was observed in the 80μg/kg/day group. Approximately two‐fold increases in platelet counts were observed at doses higher than 5 /μg/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.

Leukemia inhibitory factor reduces body fat mass in ovariectomized mice

“…The vehicle-treated OVX and SHAM mice differ substantially in baseline fat, and therefore it would have been difficult to compare the effects of LIF between these two groups. As mentioned above, LIF has exerted anti-obesity effects in various animal models (11,12), and we can now conclude that this effect can also be seen in the absence of ovarian estrogens.…”

“…In line with this, we observed a significant increase in both the total weight of dissected white fat depots and in serum leptin levels after ovariectomy in the present study. Moreover, treatment with the cytokine, LIF, can decrease body fat in various animal models (11,12).…”

“…LIF is a pleiotropic cytokine with extensive hematopoietic, neuronal, and endocrine actions (10), and it has also been reported that LIF can decrease fat mass in some animal models (11,12). The LIF receptor shares the gp130 signal mediating receptor subunit with several members of the interleukin-6 (IL-6) cytokine receptor super family (10).…”

Molecular analysis of lipid‐depleting factor in a colon‐26‐inoculated cancer cachexia model

“…18 -20,49 -51 Akiyama et al 52 reported prominent loss of adipose tissue in a monkey injected with human . Aliquots of samples were assayed using an ELISA system that detects nucleosome-associated apoptotic DNA fragments.…”

The relationship between interleukin-6 and C-reactive protein in patients with benign and malignant prostate disease

“…In cancer, the factors which determine circulating concentrations of C-reactive protein are less clear, since studies in cell lines and animal tumour models have demonstrated that a number of factors stimulate C-reactive protein production. For example, it has been shown that leukaemia inhibitory factor and ciliary neurotrophic factor are also capable of inducing an acute-phase protein response from the liver (Baumann et al, 1993;Henderson et al, 1994;Akiyama et al, 1997). There is also evidence that soluble receptor subunits involved in interleukin-6 signal transduction, the soluble interleukin-6 receptor and the soluble gp130 receptor may be important in the regulation of interleukin-6 activity and the acute-phase protein response (Narazaki et al, 1993;Jones and Rose-John, 2002).…”