Leukemia inhibitory factor (LIF) is a cytokine which was primarily described as a product of activated T lymphocytes and macrophages (3). It is a variably glycosylated 180 amino acid protein of apparent molecular weight between 35 and 67 kDa depending on its source and glycosylation. LIF is a member of a family of cytokines composed of Oncostatin-M, Interleukin 6, Interleukin 11, ciliary neurotrophic factor and granulocyte colony-stimulating factor. LIF exerts its pleiotropic functions in a wide variety of systems. Examples for its important and diverse physiological functions are support of growth and inhibition of differentiation of normal embryonic stem cells, stimulation of the production of acute-phase proteins by hepatocytes (4). LIF is able to potentiate interleukin 3 capacity to enhance megakaryocytic differentiation of myeloid progenitors and to stimulate bone resorption and new bone formation. In neural development, LIF induces an upregulation of neuropeptides and acetylcholine synthesis in sympathetic neurons and is a neurotrophic survival factor. There is furthermore emerging evidence to suggest that LIF overproduction during acute or chronic inflammatory conditions may be responsible for some of the deranged physiological manifestations of disease. A variety of human tumour lines have been shown to constitutively produce detectable levels of LIF while generally LIF expression is induced by stimulatory factors. A soluble form of LIF can be detected in human body fluids such as serum, whole blood, synovial fluid and urine, quantitative assessment of the cytokine in normal subjects and of patients suffering from a variety of diseases helps to get insight into various pathological situations. It furthermore turned out to be of crucial significance to detect the glycosyslated form of the LIF protein by usage of antibodies raised against this molecule and a glycosylated calibrator. It has been shown that levels of LIF in blood, urine and other body fluids are increased in definite biological abnormalities such as Hypercalcemia, polycythemia, erythropoietic crisis, hyperthrombocythemia; during acute rejection of allograft transplast, especially kidney; in osteoporosis. Increased plasma levels of LIF in Sepsis correlate with Shock and poor prognosis. It is also known to play a major role in human inflammatory lung diseases and generally in acute and chronic inflammations including pneumonia, Rheumatoid arthritis (serum and synovial levels elevated), carcinoma (adenocarcinoma, mesothelioma, melanoma, peritonitis. LIF concentration in the bone marrowplasma of patients with hematologic malignancies are significantly elevated. Leukemia inhibitory factor concentrations were significantly elevated in amniotic fluid in association with intraamniotic infection.

Synonyms: DIF (Differentiation-inducing factor), DIA (Differentiation-inducing activity), DRF (Differentiation-retarding factor), HSF III (Hepatocyte-stimulating factor), MLPLI (Melanoma-derived lipoprotein lipase inhibitor), HILDA (Human interleukin for DA-1 cells), CNDF (Cholinergic neuronal differentiation factor), OAL (Osteoclast-activating factor)