Terminology in endocrinology used to be pretty easy. All of the anterior pituitary hormones were isolated and named quite simply on the basis of their biological effects, although there has always been some transatlantic uneasiness about using the term trophic (which means,“to nourish”) vs. tropic (which means,“to turn to” as in the case of plants and the sun). Adrenocorticotropic, follicle stimulating, luteinizing, and thyrotropic hormones afforded no difficulty nor did GH, later named somatotropin. PRL gave problems because it stimulates milk only in mammals, and in lower forms has a wide variety of actions in water and salt metabolism and behavior. The first of the smaller proteins and peptides to be isolated also fitted in reasonably well with the general scheme—gastrin stimulated acid production by the stomach, insulin was the product of the pancreatic islet cells, antidiuretic hormone inhibited water excretion, and oxytocin stimulated uterine contraction. Even the hypothalamic hypophysiotropic hormones are appropriately named except that there are several cross-over functions; TRH could well have been called PRL-releasing factor (PRF), and somatostatin could have been named panhibin as was once suggested. But this relatively tidy scheme has gone seriously awry in the field of cytokines, which comprise a huge number of cell-derived stimulating and inhibitory factors. Although these pleiotropic factors exert important effects on metabolic, endocrine, and neural activity, most were initially recognized as factors involved in innate or acquired immunity, or as regulators of hematopoiesis, and their cardinal names often indelibly bias the way we think about their functions.“Endogenous pyrogen”(the circulating fever-causing factor induced by bacterial toxin) has mercifully been renamed interleukin-1. Interleukin-2 was first recognized as a T lymphocyte growth factor, and IL-6 was initially called B-cell differentiating factor. Tumor necrosis factor and cachectin were isolated and named on the basis of different bioassays, one that measured tumor regression after injections of bacterial toxin, and the other based on wasting and impaired fat deposition. Later they were shown to be identical molecules. And this brings us to leukemia inhibitory factor (LIF), first described a little more than a decade ago. LIF was initially identified as a product of mouse macrophages that brought about the differentiation (toward maturity) of a mouse monocytic leukemia cell line (1). The human homologue (mol wt approximately 20,000) was identified by screening a genomic library with a murine complementary DNA probe (2); the human peptide has 78% sequence identity with the mouse factor. Within 3 yr of its discovery, LIF had been shown to be identical with the cholinergic differentiation factor of myocardial cells (3), with a lipoprotein lipase inhibitory factor secreted by melanoma cells (4), and to have many cytokine-like activities including that of osteoclast stimulation (5). These properties overlap with those of several other cytokines, all of which exert their tissue effects by binding to specific class 1 cytokine receptors to form dimers of a common transducer termed gp130 (6). LIF first emerged as a pituitary secretion during studies of vascular growth regulating factors. In addition to vascular endothelial growth factor (VEGF), follicular cells of the pituitary (which secrete none of the classical pituitary hormones) were shown to secrete a factor that inhibited endothelial growth in cells derived from bovine aorta. Ferrara et al.(7), who first made this observation in 1992, proposed that LIF played a role in regulating the peculiar vascularity of the pituitary.

From this point on, Melmed and his …