Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the serum concentrations of interleukin-6 (IL-6) and two IL-6 family of cytokines (leukaemia inhibitory factor (LIF) and ciliary neurotrophic factor (CNTF) as well as IL-6 soluble receptor (sIL-6R) using an enzyme-linked immunosorbent assay (ELISA) in 66 patients with rheumatoid arthritis (RA) and 24 healthy controls. We examined a possible association between the serum levels of these peptides and RA activity according to the Mallya and Mace scoring system and Ritchie's index. We also evaluated the correlation between the serum levels of IL-6, LIF, CNTF and sIL-6R and duration of the disease and calculated sIL-6R/IL-6 ratio in RA patients and in the control group. IL-6 and sIL-6R were detectable in all 66 patients with RA and 24 normal individuals. LIF was also found in the serum of all patients with RA and in 16 (66.7%) normal individuals. In contrast CNTF was measurable only in 15 (22.7%) patients with RA and 24 (33.3%) normal individuals. The highest IL-6 and sIL-6R levels were found in the patients with Stages 3 and 4 of RA activity and the lowest in the control group. In contrast there were no statistically significant differences between the LIF and CNTF levels in RA patients and normal individuals. We found positive correlation between IL-6 and sIL-6R concentrations and Ritchie's index and a lack of such correlation with LIF and CNTF. IL-6 serum level correlated positively with the disease duration, but sIL-6R, LIF and CNTF did not. Serum sIL-6R/IL-6 ratio was significantly lower in RA patients than in healthy controls. In conclusion, an increase in the serum levels of IL-6 and sIL-6R, but not LIF and CNTF concentrations, may be useful markers for RA activity.
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PMID:Serum levels of interleukin-6 type cytokines and soluble interleukin-6 receptor in patients with rheumatoid arthritis. 988 70

We investigated the serum concentration of interleukin-6 (IL-6) and four IL-6 family cytokines - oncostatin M (OSM), leukaemia inhibitory factor (LIF), interleukin-11 (IL-11) and ciliary neurotrophic factor (CNTF) as well as IL-6 soluble receptor (sIL-6R) - using an enzyme-linked immunosorbent assay (ELISA) in 67 patients with multiple myeloma (MM) and 24 healthy controls, for a possible association between the serum levels of these peptides with disease activity and known prognostic factors. sIL-6R was detectable in all 67 and IL-6 in 65 (97%) patients. Both peptides were measurable in all healthy controls. In contrast, OSM was detectable in 30 (44.8%) MM patients and in only four (16.6%) normal individuals. The serum levels of IL-6, OSM and sIL-6R were significantly higher in MM patients compared with control group (P < 0.001, P < 0.03 and P < 0. 001 respectively). The highest concentrations of these cytokines were found in patients with progressive disease and the lowest in MM patients with stable disease and in healthy persons. LIF was detectable in four (6%), CNTF in 28 (41.8%) and IL-11 in eight (11. 9%) of the patients with MM. In the control group LIF, CNTF and IL-11 were measurable in 8.3%, 33.3% and 8.3% respectively. The serum concentration of these cytokines did not correlate either with clinical stage or with the phase of disease and was similar to those in healthy individuals. We found significant positive correlation between IL-6 levels and OSM (P < 0.001). We also observed positive correlation between beta2-M concentration and serum levels of IL-6 (P < 0.002), sIL-6R (P < 0.02) and OSM (P < 0.04) as well as a positive relationship between CRP and IL-6 (P < 0.001) and OSM (P < 0.002). In conclusion, the serum levels of IL-6, OSM and sIL-6R, but not LIF, IL-11 and CNTF, may be useful markers of MM activity.
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PMID:Circulating IL-6-type cytokines and sIL-6R in patients with multiple myeloma. 1023 12

Transection of the fimbria-fornix leads to retrograde degeneration of axotomized septal cholinergic neurons as manifested by loss of choline acetyltransferase and low-affinity nerve growth factor receptor (p75NGFR) immunoreactivity. Nerve growth factor administered into cerebral ventricles at the time of axotomy can prevent these changes, while ciliary neurotrophic factor can prevent the loss of p75NGFR immunostaining. Leukaemia inhibitory factor shares structural homologies with ciliary neurotrophic factor and has similar actions in the nervous system. Both proteins share the same signalling pathways, which involve the interleukin-6 transducing receptor components leukaemia inhibitory factor receptor beta and gp130. In this study, we compared the effects of leukaemia inhibitory factor, ciliary neurotrophic factor and nerve growth factor, administered into cerebral ventricles, on p75NGFR and choline acetyltransferase immunoreactivity in septal neurons after fimbria-fornix transection. We found that leukaemia inhibitory factor, like ciliary neurotrophic factor, prevents the loss of p75NGFR-stained medial septal neurons after fimbria-fornix axotomy, without maintaining choline acetyltransferase expression in these neurons. In addition, p75NGFR-immunostained neurons had significantly smaller mean diameter after axotomy in leukaemia inhibitory factor- and ciliary neurotrophic factor-treated animals as compared with either nerve growth factor-treated or unlesioned animals. These findings suggest that both leukaemia inhibitory factor and ciliary neurotrophic factor can prevent the axotomy-induced cell death of septal cholinergic neurons, but that, in contrast to nerve growth factor, these growth factors do not maintain the expression of choline acetyltransferase or the normal neuronal size of these injured neurons.
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PMID:Leukaemia inhibitory factor prevents loss of p75-nerve growth factor receptor immunoreactivity in medial septal neurons following fimbria-fornix lesions. 1036 99

gp130 is a signal-transducing receptor component used in common by the interleukin-6 (IL-6) family of hematopoietic and neurotrophic cytokines, including IL-6, IL-11, leukemia-inhibitory factor, ciliary neurotrophic factor, oncostatin-M, and cardiotrophin-1. We have examined in this study a role of gp130 in the nervous system by analyzing developmental cell death of several neuronal populations and the differentiation of astrocytes in gp130-deficient mice. A significant reduction was observed in the number of sensory neurons in L5 dorsal root ganglia and motoneurons in the facial nucleus, the nucleus ambiguus, and the lumbar spinal cord in gp130 -/- mice on embryonic day 18.5. On the other hand, no significant neuronal loss was detectable on day 14.5, suggesting a physiological role of gp130 in supporting newly generated neurons during the late phase of development when naturally occurring cell death takes place. Moreover, expression of an astrocyte marker, GFAP, was severely reduced in the brain of gp130 -/- mice. Our data demonstrate that gp130 expression is essential for survival of subgroups of differentiated motor and sensory neurons and for the differentiation of major populations of astrocytes in vivo.
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PMID:Developmental requirement of gp130 signaling in neuronal survival and astrocyte differentiation. 1037 52

The generation of diverse types of neural cells during development occurs through the progressive restriction of the fate potential of neuroepithelial progenitor cells. This process is controlled by factors intrinsic and extrinsic to the cell. While the effect of extrinsic cues on multipotent stem cells of the murine central nervous system (CNS) is becoming clearer, little is known of neural stem cells of human origin. We sought to establish the roles played by two cytokines, leukemia inhibitory (LIF) and ciliary neurotrophic factor (CNTF), and by nerve growth factor (NGF) and platelet-derived growth factor (PDGF) in regulating neuronal and astroglial differentiation in cultured embryonic diencephalic human stem cells. While NGF did not influence either neuronal or glial formation, PDGF surprisingly decreased the percentage of stem cell-generated neurons, an effect opposite to that observed in murine progenitors. Furthermore, while we confirmed the known ability of LIF and CNTF to support astroglial differentiation, we also observed that, in contrast with their murine counterparts, the fraction of CNS stem cell-generated neurons in human cultures was enhanced twofold in the presence of both cytokines. These findings highlight important differences between humans and rodents in regard to the way epigenetic cues regulate the function of neural stem cells.
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PMID:Regulation of neuronal differentiation in human CNS stem cell progeny by leukemia inhibitory factor. 1065 1

1. Leukaemia inhibitory factor (LIF) is a 180 amino acid single-chain protein, named after its effect on haematopoietic cells. Leukaemia inhibitory factor belongs to a group of cytokines that includes ciliary neurotrophic factor, interleukin (IL)-6, IL-11, cardiotrophin-1 and oncostatin M. All group members use the gp130 signal transducing subunit for intracellular signalling, but show differences in biological effect. 2. Research over the past 6-8 years has shown LIF to have potent neuromuscular activity. In vitro and in vivo studies on axotomy and nerve crush models demonstrate a powerful effect of LIF in enhancing the survival of both motor and sensory neurons, while reducing denervation-induced muscle atrophy. In models of both axotomy induced neuronal death and in the wobbler mouse, LIF is active at doses as low as 1 microgram/kg delivered systemically. 3. In muscle, LIF will increase the rate of muscle regeneration in vivo when applied exogenously after injury and will stimulate intrinsic muscle repair following its targeted release to dystrophic muscle in the mdx mouse. Leukaemia inhibitory factor may also have a role as an adjunct to myoblast transfer therapy, with studies showing that the transplantation of genetically competent myoblasts into mdx mouse muscle is enhanced when cells are injected with LIF. 4. Distribution and pharmacokinetic studies have been conducted in primates with doses of 20 micrograms/kg recombinant human LIF given subcutaneously over 2 weeks tolerated without major side effects. 5. A pharmaceutical form of recombinant human LIF (AM424; AMRAD Operations, Richmond, Victoria, Australia) entered human clinical trials during 1997 and a phase I clinical trial in healthy volunteers has been completed. A phase I repeat dose study has also been completed in cancer patients undergoing chemotherapy. The primary indication for a phase II study is the treatment of chemotherapy induced peripheral neuropathy. Other potential indications include muscle wasting diseases, acute nerve trauma and motor neuron disease. 6. The role of LIF in modulating nerve loss should make it an ideal candidate for the treatment of a number of neurological conditions. The phase I study represents the first trial in a programme for the clinical development of AM424.
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PMID:AM424: history of a novel drug candidate. 1087 17

Bone tissue is continually being remodelled according to physiological circumstances. Two main cell populations (osteoblasts and osteoclasts) are involved in this process, and cellular activities (including cell differentiation) are modulated by hormones, cytokines and growth factors. Within the last 20 years, many factors involved in bone tissue metabolism have been found to be closely related to the inflammatory process. More recently, a cytokine family sharing a common signal transducer (gp130) had been identified, which appears to be a key factor in bone remodelling. This family includes interleukin 6, interleukin 11, oncostatin M, leukaemia inhibitory factor, ciliary neurotrophic factor and cardiotrophin-1. This paper provides an exhaustive review of recent knowledge on the involvement of gp130 cytokine family in bone cell (osteoblast, osteoclast, etc.) differentiation/activation and in osteoarticular pathologies.
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PMID:gp130 Cytokine family and bone cells. 1102 60

Interleukin (IL)-6-type cytokines are multifunctional proteins involved in cardiac hypertrophy and myocardial protection. Recent studies, performed on animal models, report the production of these cytokines by heart. The aim of this study was to analyse the capacity of myocytes and fibroblasts isolated from human atrium to secrete IL-6, leukaemia inhibitory factor (LIF), cardiotrophin-1 (CT-1), IL-11, oncostatin M (OSM), ciliary neurotrophic factor (CNTF) and the soluble receptor subunits sIL-6R and sgp130 during primary culture. We detected LIF, IL-11, sgp130 and a large amount of IL-6, but not OSM, CT-1, CNTF nor IL-6R in these culture supernatants. Both cardiomyocytes and fibroblasts are able to spontaneously produce IL-6. The increase of IL-6 production all along the culture period appears to be the consequence of fibroblast proliferation and gp130 stimulation. This is the first demonstration that human cardiac cells are able to secrete IL-6, but also LIF and IL-11 in vitro. These cytokines could be involved in an autocrine and/or a paracrine networks regulating myocardial cyto-protection, hypertrophy and fibrosis.
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PMID:Secretion of IL-6, IL-11 and LIF by human cardiomyocytes in primary culture. 1212 42

The IL (interleukin)-6-type cytokines IL-6, IL-11, LIF (leukaemia inhibitory factor), OSM (oncostatin M), ciliary neurotrophic factor, cardiotrophin-1 and cardiotrophin-like cytokine are an important family of mediators involved in the regulation of the acute-phase response to injury and infection. Besides their functions in inflammation and the immune response, these cytokines play also a crucial role in haematopoiesis, liver and neuronal regeneration, embryonal development and fertility. Dysregulation of IL-6-type cytokine signalling contributes to the onset and maintenance of several diseases, such as rheumatoid arthritis, inflammatory bowel disease, osteoporosis, multiple sclerosis and various types of cancer (e.g. multiple myeloma and prostate cancer). IL-6-type cytokines exert their action via the signal transducers gp (glycoprotein) 130, LIF receptor and OSM receptor leading to the activation of the JAK/STAT (Janus kinase/signal transducer and activator of transcription) and MAPK (mitogen-activated protein kinase) cascades. This review focuses on recent progress in the understanding of the molecular mechanisms of IL-6-type cytokine signal transduction. Emphasis is put on the termination and modulation of the JAK/STAT signalling pathway mediated by tyrosine phosphatases, the SOCS (suppressor of cytokine signalling) feedback inhibitors and PIAS (protein inhibitor of activated STAT) proteins. Also the cross-talk between the JAK/STAT pathway with other signalling cascades is discussed.
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PMID:Principles of interleukin (IL)-6-type cytokine signalling and its regulation. 1277 95

Variations in the expression of cytokines from the interleukin-6 (IL-6) family: ciliary neurotrophic factor (CNTF), leukaemia inhibitory factor (LIF), and cardiotrophin 1 (CT-1) were studied during cardiac remodelling leading to left ventricular hypertrophy (LVH) in TGR(mRen2)27 rats at the age of 8 and 20 weeks. The cytokines mRNA levels within the free wall of the left ventricle were measured by semi-quantitative RT-PCR standardised with 18S. They were compared between heterozygous rats for the mRen2 transgene (TG+/-) and control rats (TG-/-). No significant difference was observed between results obtained at 8 and 20 weeks of age. At 20 weeks of age, TGR(mRen2)27 rats showed higher levels of mRNA LIF and IL-6 respectively by 52 and 55% compared to the control rats [LIF TG+/-: 3.17 +/- 0.21, TG-/-: 2.09 +/- 0.03; p < 0.001; n = 5; and IL-6 TG+/-: 1.53 +/- 0.13; TG-/-: 0.99 +/- 0.17; p < 0.05; n = 5]. By contrast, no variation of mRNAs levels of CT-1 and gp 130 genes was observed between control and transgenic rats. Concerning the cytokine receptors, the levels of mRNA for IL-6R did not vary while those of receptor subunits LIFR and CNTFR were decreased respectively by 48 and 42% in transgenic rats vs controls [LIFR TG+/-: 0.48 +/- 0.01; TG-/-: 0.92 +/- 0.08 p < 0.001; n = 5; and CNTFR TG+/-: 1.07 +/- 0.08; TG-/-: 1.85 +/- 0.18; p < 0.01; n = 5]. Therefore, these results show a specific pattern of activation of the cytokines pathway in the LVH of the TGR(mRen2)27 rat.
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PMID:[Expression of cytokines and their receptors in left ventricular hypertrophy in TGR(mRen2)27 rats]. 1294 31


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