Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this study, we investigated the effect of recombinant human interleukin-6 (IL-6) on colony-forming cells for granulocytes and macrophages (CFU-GM) cultured in suspension. IL-6 when used alone did not induce proliferation of highly purified CD34+ human hematopoietic progenitors. Moreover, no influence of IL-6 was observed on the proliferation induced by granulocyte-macrophage colony-stimulating factor (GM-CSF) or granulocyte (G)-CSF. However, a marked survival enhancement (GM-CSF 228 +/- 42%, p < 0.01, and G-CSF 137 +/- 9%, p < 0.05) was observed when CD34+ cells were preincubated with IL-6 for 6 days. This survival effect became even more pronounced under serum-poor conditions (GM-CSF 380 +/- 80%, p < 0.01, and G-CSF 180 +/- 20%, p < 0.01) and could also be demonstrated at the single cell level in a colony-forming assay. By analysis of subpopulations of CD34+ bone marrow (BM) cells selected on the basis of CD45RO expression, the observed IL-6-mediated survival effect was found to be restricted to the CFU-GM containing CD45RO- subset. Our data show that IL-6 is a survival factor for CFU-GM.
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PMID:Interleukin-6 is a survival factor for committed myeloid progenitor cells. 769 39

It has been hypothesized that interleukin-6 (IL-6) and granulocyte-colony-stimulating factor (G-CSF) may fold as four-alpha-helix bundle proteins. To probe the functional role of the putative fourth helical segment of IL-6 (D-helix), a chimeric IL-6/G-CSF analog containing the predicted D-helix of G-CSF as well as a panel of IL-6 D-helix point mutants were analyzed for their respective secondary structure, antigenicity, and receptor binding and biological activities. The putative D-helix of IL-6 could not be replaced by its G-CSF counterpart in spite of their high degree of similarity and thus is indispensable for the antigenic and functional integrity of the IL-6 receptor binding site. Conversely, the grafting of the G-CSF D-helix did not confer any G-CSF activity to IL-6. A synthetic helical peptide containing the IL-6 D-helix was inactive, even when mixed with or linked to a peptide from the A-helix known to be involved in the active site. However, the conserved residues F173, R179, and R182 found in the D-helices of both IL-6 and G-CSF critically contribute to the architecture of the IL-6 active site. Indeed, mutation of F173 or R179 markedly affected IL-6 receptor binding and biological activities, but not the conformation of a major neutralization epitope. Furthermore, substitution of R182 resulted in a significant unfolding of the D-helix accompanied by a drastic loss in IL-6 antigenicity and functional activities. Nevertheless, residues other than F173, R179, and R182 also contribute to IL-6 specificity.
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PMID:Structure-function analysis of the C-terminal segment of human interleukin-6. 769 65

A young Italian woman with a POEMS syndrome is described. The patient had a plasma cell dyscrasia without clinical or laboratory evidence of multiple myeloma. The phenotypic analysis of bone marrow cells and peripheral blood lymphocytes revealed a normal pattern. The immunological study of CSF showed high levels of interleukin-6, whereas this cytokine was not detectable in the serum. Electrophysiological studies and sural nerve biopsy showed a mixed, demyelinating-axonal sensorimotor neuropathy with marked loss of large myelinated fibres. Long-term treatment with prednisone gave some clinical improvement.
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PMID:POEMS syndrome: clinical, pathological and immunological study of a case. 770 42

Recent investigations have revealed the involvement of cytokines in the pathogenesis of psoriasis. This study examined the amount of inflammatory cytokines--interleukin-1 (IL-1), interleukin-6 (IL-6) and granulocyte macrophage colony-stimulating factor (GM-CSF)--released into the supernatants of organ cultures of involved and uninvolved skin from psoriatic patients and normal skin from healthy individuals. Bioassays were employed to detect the activities of IL-1 and IL-6. Enzyme-linked immunosorbent assay (ELISA) methods were used to quantitate immunoreactive IL-1 alpha, IL-1 beta, IL-6 and GM-CSF. The activity of IL-1 in uninvolved psoriatic skin was found to be increased relative to that in involved and normal skin, while immunoreactive IL-1 beta was found only in involved skin. A neutralization experiment showed that bioactive IL-1 was mostly attributable to IL-1 alpha. Uninvolved psoriatic skin also secreted higher amounts of both bioactive and immunoreactive IL-6 compared with involved skin. Immunoreactive GM-CSF was detected in uninvolved skin only. These cytokines detected in uninvolved skin may have been released from epidermal or mesenchymal cells, since uninvolved skin contained fewer inflammatory infiltrates. Our results offer additional evidence that increased amounts of inflammatory cytokines in uninvolved skin may provide a preliminary condition and play important roles in the initial events in the evolution of psoriatic lesions.
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PMID:Detection of inflammatory cytokines in psoriatic skin. 776 87

The chemokines, macrophage inflammatory protein-1 (MIP-1) and its subunit MIP-1 beta, induce an intense fever in the rat when they are injected directly into the anterior hypothalamic, pre-optic area (AH/POA), a region containing thermosensitive neurons. The purpose of this study was to compare the central action on body temperature (Tb) of MIP-1 beta with that of interleukin-6 (IL-6), which also has been implicated in the cerebral mechanism underlying the pathogenesis of fever. Following the stereotaxic implantation in the AH/POA of guide cannulae for repeated micro-injections, radio transmitters which monitor Tb continuously were inserted intraperitoneally in each of 15 male Sprague-Dawley rats. Each micro-injection was made in a site in the AH/POA in a volume of 1.0 microliter of pyrogen-free artificial CSF, recombinant murine MIP-1 beta, or recombinant human IL-6. MIP-1 beta in a dose of 25 pg evoked an intense fever characterized by a short latency, a mean maximum rise in Tb of 2.4 +/- 0.21 degrees C reached by 3.7 +/- 0.42 hr, and a duration exceeding 6.5 hr. Injected into homologous sites in the AH/POA, IL-6 induced a dose dependent fever of similar latency and a mean maximal increase in Tb of 1.2 +/- 0.25 degrees C, 1.8 +/- 0.15 degrees C, and 2.1 +/- 0.22 degrees C and duration of 6.2 +/- 1.28 hr, 6.7 +/- 0.49 hr, and 6.8 +/- 0.65 hr when given in doses of 25, 50, and 100 ng, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Fever and feeding in the rat: actions of intrahypothalamic interleukin-6 compared to macrophage inflammatory protein-1 beta (MIP-1 beta). 780 90

Interleukin-6 (IL-6) can alter brain function after peripheral administration, suggesting that it, like IL-1 alpha, IL-1 beta and TNF-alpha, might be able to cross the blood-brain barrier (BBB). We used multiple-time regression analysis to measure the unidirectional influx constant (Ki) into brain of radioactively labeled murine and human IL-6 given i.v. Ki values ranged from 3.05 to 4.54 (10(-4)) ml/g/min and were inhibited by unlabeled IL-6 but not IL-1 alpha or TNF-alpha, showing that the transport system for IL-6 is distinct from those for IL-1 alpha and TNF-alpha. Approximately 0.2% of the dose injected i.v. entered each gram of brain. The capillary depletion method showed that most of the IL-6 taken up by brain entered the parenchyma. However, only approximately 16% of the radioactivity recovered eluted as intact I-IL-6 in brain and approximately 50% in CSF after chromatographic separation by HPLC/Sephadex. The efflux rate for IL-6 injected into the lateral ventricle of the brain suggests that it enters the blood with the reabsorption of CSF. These results suggest that blood-borne IL-6 can reach sites behind the BBB, but that susceptibility to enzymatic degradation may limit contact time within the CNS.
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PMID:Penetration of interleukin-6 across the murine blood-brain barrier. 784 24

A replication-defective recombinant retrovirus containing the human papilloma virus E6/E7 genes (LXSN-16 E6E7) was used to immortalize stromal cells from human marrow. The E6/E7 gene products interfere with the function of tumor-suppressor proteins p53 and Rb, respectively, thereby preventing cell cycle arrest without causing significant transformation. Twenty-seven immortalized clones designated HS-1 to HS-27 were isolated, four of which are characterized in this report. Two cell lines, HS-5 and HS-21, appear to be fibroblastoid and secrete significant levels of granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage-CSF (GM-CSF), macrophage-CSF (M-CSF), Kit ligand (KL), macrophage-inhibitory protein-1 alpha, interleukin-6 (IL-6), IL-8, and IL-11. However, only HS-5 supports proliferation of hematopoietic progenitor cells when cocultured in serum-deprived media with no exogenous factors. Conditioned media (CM) from HS-5 promotes growth of myeloid colonies to significantly greater extent than a cocktail of recombinant factors containing 10 ng/mL of IL-1, IL-3, IL-6, G-CSF, GM-CSF, and KL and 3 U of erythropoietin (Epo). Two additional clones, HS-23 and HS-27, resemble "blanket" cells, with an epithelioid morphology, and are much larger, broader, and flatter when compared with HS-5 and HS-21. These lines secrete low levels of growth factors and do not support proliferation of isolated progenitor cells in cocultures. CM from HS-23 and HS-27 also fail to support growth of myeloid colonies. Both HS-23 and HS-27 express relatively high levels of VCAM-1, yet HS-27 is the only line that supports the formation of "cobblestone" areas by isolated CD34+38lo cells. We hypothesize that HS-5, HS-21, HS-23, and HS-27 represent functionally distinct components of the marrow microenvironment.
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PMID:Functionally distinct human marrow stromal cell lines immortalized by transduction with the human papilloma virus E6/E7 genes. 784 21

A 52-year-old Caucasian man treated with granulocyte-macrophage colonystimulating factor (GM-CSF) developed a cutaneous eruption on legs and ankles with clinical and histologic features of erythema multiforme. Laboratory studies indicated that the eruption occurred at the time of peripheral blood lymphocyte recovery and that it was coincidental with serum peaks of interleukin-1 (IL-1), interleukin-2 (IL-2), interleukin-6 (IL-6) and tumour necrosis factor-alpha. We postulate that GM-CSF provoked erythema multiforme in a predisposed individual as a consequence of either an inappropriate cytokine secretion or of an abnormal amplification mechanism following lymphocyte recovery.
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PMID:Erythema multiforme during GM-CSF therapy. 791 20

Cells of monocytic lineage (Mo) persistently infected with human immunodeficiency virus (HIV) have been suspected to be a major reservoir for in vivo transmission of virus to susceptible target cells. Cellular events and mechanisms that upregulate viral gene expression in such cells are important issues. Because the traffic of such cells is central to biodistribution of HIV, we have explored the impact of interaction of endothelium with HIV-1-infected U1 promonocytic cells. Coculturing of U1 with human umbilical endothelial cells (HUVEC) for 24 to 72 hours in the absence of stimulation induced HIV-1 p24 biosynthesis significantly. Antibody-blocking experiments indicated that CD11/CD18 integrins play a role in upregulation of HIV expression elicited by interaction with HUVEC. Engagement of CD11b/CD18 by adherence of U1 to surfaces coated with either the cognate ligand fibrinogen or monoclonal antibody specific for CD11b/CD18 also enhanced p24 biosynthesis. Furthermore, endothelial cells were found to constitutively synthesize and secrete soluble factors that enhanced HIV-1 synthesis. The enhancing factors, of estimated size 10 to 45 kD, were induced in HUVEC to high levels by monokines or by lipopolysaccharide, resulting in markedly enhanced HIV-1 expression by U1. These endothelial cell-derived HIV-1-enhancing factors consist of, among others, interleukin-6 (IL-6), IL-1 beta, and granulocyte-macrophage CSF (GM-CSF). Our results suggest that activation of HIV biosynthesis in infected Mo via interaction with endothelium may impact significantly on the tissue distribution and pathogenesis of HIV infections.
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PMID:Upregulation of human immunodeficiency virus-1 in chronically infected monocytic cell line by both contact with endothelial cells and cytokines. 791 48

Tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and granulocyte monocyte-colony stimulating factor (GM-CSF) were measured in serum and involved and uninvolved skin blister fluids of 20 psoriatic patients and 10 healthy subjects, by enzyme immunoassay. TNF-alpha and IL-6 were always detectable in involved skin blister fluids, while GM-CSF was detected only in 45% of these samples. TNF-alpha, IL-6 and GM-CSF were detected in 95, 100 and 10% of uninvolved skin blister fluid samples, respectively. TNF-alpha and IL-6 were found in 50 and 30% of control blister fluids, while GM-CSF was never detected. In serum, TNF-alpha was detected in 75% of patients and in 70% of controls; IL-6 in 45% of patients and in no controls; and GM-CSF in 35% of patients and in 20% of the controls. The median TNF-alpha and IL-6 levels in involved skin were statistically higher than those of both uninvolved and control skin blister fluids. TNF-alpha and IL-6 levels in blister fluids obtained from both involved and uninvolved skin were higher than those of the patients' sera. GM-CSF, when present in involved skin blister fluids, showed correlated levels with the other cytokines (TNF-alpha: R = 0.85, P = 0.004; IL-6: R = 0.72, P = 0.03). TNF-alpha was highly correlated with IL-6 (R = 0.78, P < 0.00001) in involved skin blister fluids. TNF-alpha and IL-6 levels of involved skin blister fluids showed significant correlations with the psoriasis area and severity index scores in the patients, suggesting a direct relationship between these cytokines and the clinical manifestations of the disease. Moreover, the TNF-alpha levels were particularly related to the erythema scores in the patients, further supporting evidence of their role in the pathogenesis of the disease.
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PMID:Correlated increases of tumour necrosis factor-alpha, interleukin-6 and granulocyte monocyte-colony stimulating factor levels in suction blister fluids and sera of psoriatic patients--relationships with disease severity. 795 93


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