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LIF: Not Just a Leukemia Inhibitory Factor^*

Department of Clinical Immunology and Biological Therapy, The University of Texas M.D. Anderson Cancer Center Houston, Texas 77030

Correspondence: Address requests for reprints to: Razelle Kurzrock, M.D., Department CIBT, Box 41, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030.

Abstract

I. Introduction: LEUKEMIA inhibitory factor (LIF) is a pleiotropic cytokine with the ability to influence the function and/or development of seemingly unrelated body elements (Table 1): blood cells, embryonal cells, hepatocytes, neurons, adipose tissues, and bone. These diverse properties account for the bewildering array of names under which this factor has been published (Table 2). Although the most common designation is leukemia inhibitory factor, this molecule can promote both suppression and stimulation of proliferation and/or differentiation depending on the leukemic cell line examined. In addition, LIF may serve as part of the body's energy storage communication network. In this regard, some of the abnormalities that manifest in mammalian hosts with chronic illness include increased serum acute phase proteins and a wasting diathesis accompanied by hypertriglyceridemia; the latter is caused by suppression of lipoprotein lipase, the key enzyme of triglyceride metabolism. It is therefore of interest that LIF induces cachexia in mice, inhibits lipoprotein lipase, and stimulates hepatocyte release of acute phase proteins. In a different arena, the potent effects of LIF on embryonal stem cells suggest a critical role for this molecule in the earliest stages of embryogenesis. Finally, LIF also promotes remodeling of bone and functions as a neuronal differentiation factor. It remains unclear how one molecule can affect distinct organ systems without simultaneous side effects on its other target tissues, although recent data demonstrating that LIF exists both as a diffusible form and a form incorporated into the extracellular matrix (18) suggest that immobilization may serve to restrict its spheres of influence. In this review, we will discuss the multifaceted aspects of LIF functions and implications for understanding the cytokine network.

Footnotes

^* Research conducted, in part, by the Clayton Foundation for Research. Dr. Gutterman is a Senior Clayton Foundation Investigator.

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