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)

Interleukin-6 (IL-6) was demonstrated to be a strong autocrine or paracrine plasmocytoma cell growth factor in humans. Using a bioassay, high serum IL-6 (S-IL-6) levels were correlated with disease severity in plasma cell dyscrasias. Since other cytokines could interfere with the bioassays, we developed a specific radioimmunoassay to study S-IL-6 levels in 102 patients with monoclonal gammopathy (MG). S-IL-6 level was studied by a double antibody radioimmunoassay using a rabbit polyclonal anti-IL-6 antibody and a human recombinant IL-6 as the standard. The lowest value of the standard significantly different from zero was found to be 78 pg/ml. Within-run and between-run precisions were characterized by a mean coefficient of variation of 3.72 and 5.5%, respectively. The mean analytical recovery was found to be 113% and the immunochemical identity of IL-6 standard and S-IL-6 was shown by dilution tests. IL-6 was detected in all tested sera. Sera from 66 healthy volunteers and 43 patients with acute leukemia or malignant lymphoma were tested as controls. In healthy subjects, S-IL-6 values were 294 +/- 86 pg/ml. MG were classified as multiple myeloma (MM), macroglobulinemia, and MG of undetermined significance (MGUS). The distribution of S-IL-6 levels in patients with MG was significantly higher than in healthy subjects but lower than in patients with acute leukemia or Hodgkin's lymphoma. Results obtained in 55 patients with MM were related to other biological parameters. S-IL-6 levels correlated with bone-marrow plasmacytosis (P less than .0005), serum-lactate dehydrogenase (S-LDH; P less than .005), serum beta 2 microglobulin (S -beta 2m; P less than .01), and serum calcium (S-Ca; P less than .025) and inversely correlated with haemoglobin (P less than .025). Our results indicate that 1) radioimmunoassay is suitable for the measurement of human IL-6 in serum; 2) high S-IL-6 levels are observed in a small number of patients with MG; and 3) S-IL-6 level correlates with tumour cell mass in patients with overt MM.
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PMID:Radioimmunoassay for the measurement of serum IL-6 and its correlation with tumour cell mass parameters in multiple myeloma. 154 13

An acute (2 h) exposure of humans to 0.4 ppm ozone initiates biochemical changes in the lung that result in the production of components mediating inflammation and acute lung damage as well as components having the potential to lead to long-term effects such as fibrosis. However, many people are exposed to lower levels of ozone than this, but for periods of several hours. Therefore, it is important to determine if a prolonged exposure to low levels of ozone is also capable of causing cellular and biochemical changes in the lung. Nonsmoking males were randomly exposed to filtered air and either 0.10 ppm ozone or 0.08 ppm ozone for 6.6 h with moderate exercise (40 liters/min). Bronchoalveolar lavage (BAL) was performed 18 h after each exposure, and cells and fluid were analyzed. The BAL fluid of volunteers exposed to 0.10 ppm ozone had significant increases in neutrophils (PMNs), protein, prostaglandin E2 (PGE2), fibronectin, interleukin-6 (IL-6), and lactate dehydrogenase (LDH) compared with BAL fluid from the same volunteers exposed to filtered air. In addition, there was a decrease in the ability of alveolar macrophages to phagocytize yeast via the complement receptor. Exposure to 0.08 ppm ozone resulted in significant increases in PMNs, PGE2, LDH, IL-6, alpha 1-antitrypsin, and decreased phagocytosis via the complement receptor. However, BAL fluid protein and fibronectin were no longer significantly elevated. We conclude that exposure of humans to as low a level as 0.08 ppm for 6.6 h is sufficient to initiate an inflammatory reaction in the lung.
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PMID:Exposure of humans to ambient levels of ozone for 6.6 hours causes cellular and biochemical changes in the lung. 184 79

Recombinant human interleukin-6 (rhIL-6) is a pluripotent cytokine with proinflammatory, antitumor, and growth factor effects. Clinical investigations of rhIL-6 either alone as immunotherapy or as a colony-stimulating factor in conjunction with chemotherapy have shown a dose-dependent, rapid onset, and largely reversible decrease in venous hematocrit levels. In an effort to determine the mechanism for the rhIL-6-associated anemia, we measured red blood cell volume serially in patients receiving rhIL-6 at either 30 micrograms/kg/day as a 120-hour continuous intravenous infusion (renal cell carcinoma) or 100 micrograms/kg/d intravenously over 1 hour for 5 days (melanoma) as part of two separate phase II trials. Radioisotope dilution assays with 51Cr-labeled autologous red blood cells and hemolysis screens were performed on day 1 before the initiation of therapy and on day 5 shortly before the end of therapy. In the 6 patients studied, the mean decrease in hemoglobin concentration was 1.9 +/- 0.94 g/dL. The mean decrease in the hematocrit level was 6% +/- 2% and the mean increase in total blood volume was 731 +/- 337 mL. These changes were explained by a mean decrease in red blood mass of 106 +/- 109 mL and a mean increase in plasma volume of 743 +/- 289 mL. The decrease in red blood cell mass was largely explained by phlebotomy during the hospitalization, but was not statistically significant (paired t-test, P = .06). All other changes were statistically significant (P < .05). Simple regression analysis indicated that the decrease in hematocrit level and increase in plasma volume were related (y = -1.78 - .0066X; R = -.74). Measurements of lactate dehydrogenase, bilirubin, haptoglobin, and reticulocyte counts and serial stool hemoccults did not indicate hemolysis or blood loss. We conclude that the anemia caused by IL-6 is caused by an increase in plasma volume.
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PMID:Interleukin-6-associated anemia: determination of the underlying mechanism. 763 34

Mice of the C57BL/6 strain were injected with bacterial lipopolysaccharide (LPS) followed by formylnorleucyl-leucyl-phenylalanine (FNLP) by the intraperitoneal route; markers of acute lung injury were examined in mice given a fusion protein of soluble human tumor necrosis factor-alpha (TNF-alpha) receptor (p80) linked to the Fc portion of human IgG (TNFR:Fc) or excipient. Challenge with LPS/FNLP elicited an adult respiratory distress syndrome-like pathology characterized by sharp increases in levels of lactate dehydrogenase (LDH) and total proteins in bronchoalveolar lavage as well as in lung myeloperoxidase (MPO) content at 16 and 20 h after challenge. Infusion of 1 mg of TNFR:Fc 2 h before challenge very significantly abrogated the increases in LDH, protein levels, and MPO. Histologic analysis revealed that LPS/FNLP infusion resulted in an intravascular neutrophil agglomerate and perivascular/peribronchial damage; the extent of tissue lesions was significantly reduced, but not abrogated, by TNF-alpha depletion. There were moderate levels of antigenic TNF-alpha in lung homogenates at 16 and 20 h after challenge, not affected by infusion with TNFR:Fc. No bioactive TNF-alpha was detected in lung homogenates of challenged mice given TNFR:Fc. High levels of antigenic interleukin-6 (IL-6) were found in lung homogenates of challenged mice treated with TNFR:Fc or with diluent. Elevated levels of antigenic IL-6 and TNF-alpha were found in sera of challenged mice at 16 and 20 h after injection; TNFR:Fc-treated mice had a higher level of antigenic TNF-alpha than did challenged mice given diluent, but it was not bioactive.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A mouse model of lung injury induced by microbial products: implication of tumor necrosis factor. 800 42

Activins, members of a family of the transforming growth factor beta (TGF beta), are involved in the regulation of multiple biological events. We found a novel effect of activin A on hybridoma and myeloma cell lines. Activin A exhibited a cytotoxic effect on interleukin-6 (IL-6)-dependent B9 cells and induced a significant increase in the proportion of fragmented DNA. B9 cells exposed to activin A released high amounts of lactate dehydrogenase (LDH) and exhibited the typical ladder pattern of DNA fragmentation of apoptotic cells. IL-6 did not prevent apoptosis of B9 cells induced by activin A. The cytotoxicity of activin A to B9 cells was suppressed by follistatin. On the other hand, TGF beta showed no cytotoxic effect on B9 cells. These findings indicate that apoptosis induced by activin A could be one of the mechanisms to prevent uncontrolled cell growth.
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PMID:Activin A induces apoptotic cell death. 826 37

Solutions were formulated to examine, independently, the roles of osmolality and glucose in the reduction of viability and inhibition of phagocyte function by dextrose-containing peritoneal dialysis fluids. The exposure of neutrophils (polymorphonuclear leukocytes) to test fluids containing > or = 2.7% (wt/vol) glucose resulted in significant cytotoxicity as assessed by the release of lactate dehydrogenase above control values (7.12 +/- 2.65%). At the highest concentration of glucose (4.5%), lactate dehydrogenase release was 15.83 +/- 0.49% (P < 0.05). These effects were directly related to the presence of D-glucose in the test fluids. In contrast, phagocytosis and the release of leukotriene B4 from PMN stimulated with serum-treated zymosan were significantly inhibited in an osmolality-, but not glucose-, dependent manner. The inhibition of tumor necrosis factor alpha and interleukin-6 release from mononuclear leukocytes was inhibited by a combination of osmolality and monosaccharide concentration. Under the same conditions, PMN respiratory burst activation remained unaffected irrespective of glucose concentration or fluid osmolality. These data indicate that, in addition to the low pH of peritoneal dialysis fluid and its high lactate concentration, its glucose content (either directly or as a consequence of the resulting hyperosmolality of the fluid) inhibits cell functional parameters. These findings suggest clinically significant inhibition of host defense mechanisms because, in high-glucose dialysis fluids, osmolality does not reach physiologic values, even during extended intraperitoneal dwell periods.
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PMID:Peritoneal dialysis fluid inhibition of phagocyte function: effects of osmolality and glucose concentration. 838 31

The release of free radicals and pro-inflammatory cytokines such as nitric oxide (NO) and tumor necrosis factor alpha (TNF alpha) is commonly observed in adult respiratory distress syndrome (ARDS) following infection or exposure to microbial products. The aim of this study was to scrutinize the involvement of NO in ARDS in a mouse model determined by the sequential exposure to lipopolysaccharide (LPS) and formyl-norleucyl-phenylalanine (FNLP). Nitrite measurements in bronchoalveolar lavage fluids (BALF) and sera demonstrated that exposure to microbial products elicits large amounts of NO in LPS/FNLP-challenged mice. This release was significantly inhibited by infusion with the inducible NO synthase antagonist, aminoguanidine (AG). Our results show that LPS/FNLP exposure induces lung damage as demonstrated by protein and lactate dehydrogenase (LDH) increases in BALF. Liver damage was also detected in LPS/FNLP-challenged mice with increases in serum ornithine-carbamoyltransferase (OCT) levels. LPS/FNLP infusion led to elevated levels of the cytokines interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF alpha) in the sera. LPS/FNLP also led to neutrophil adhesion in the lung vasculature, as seen by increased levels of myeloperoxydase. Interestingly, inhibition of NO release in challenged mice led to an important increase in markers of tissue damage in the lungs and livers, but a decrease in neutrophil recruitment. Infusion of AG in LPS/FNLP-challenged mice led to a much increased level of sera TNF alpha. These data suggest that after exposure to microbial products, NO generated as a result of activation of the inducible NO synthase blocks the full expression of tissue damage in the lungs.
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PMID:The involvement of nitric oxide in a mouse model of adult respiratory distress syndrome. 854 74

The legal procedure for evaluating the toxicity of cosmetic, household, chemical and pharmaceutical products is still the irritancy Draize test on rabbits. Various irritation tests are currently being developed as alternatives to in vivo animal testing. Our in vitro model system is composed of 24 equivalent dermis (ED) comprising a chitosan-cross-linked collagen-glycosaminoglycan matrix populated by foreskin fibroblasts. In evaluating this system for irritancy testing, three different measures of toxicity were used: MTT (dimethylthiazol diphenyltetrazolium bromide) reduction, and lactate dehydrogenase and interleukin-6 release. The experiments described herein represent a preliminary evaluation to determine the usefulness and predictive value of our 24 ED kit as an alternative method for the prediction of human dermal reaction, versus three chemical products: cadmium chloride, lauryl sulfate, and benzalkonium chloride. Preliminary results suggest that the ED may be a useful in vitro model for the prediction of cutaneous and ocular toxicity and allow the development of a 24-skin-equivalent kit realized by seeding human normal keratinocytes onto the equivalent dermis.
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PMID:Pharmacotoxicological applications of an equivalent dermis: three measurements of cytotoxicity. 856 46

Inclusion complexes of gamma-cyclodextrin and octamethylcyclotetrasiloxane (D4), decamethyltetrasiloxane (M10TS), and 1,3,5,7-tetramethyltetravinylcyclotetra - siloxane (TMTV-D4) were prepared to compare the cytotoxic effects of siloxanes in vitro. In these preparations, the hydrophobic siloxanes are surrounded by a hydrophilic shell of eight circularly linked D-glucose molecules (gamma-cyclodextrin), and upon contact with plasma membranes the siloxane molecule can intercalate into the lipid bilayer of the cell membrane. XRPC24, 2-11 plasmacytoma, CH12.LX lymphoma and P388D1 macrophage-like cells were used as indicator cells in toxicity assays. Using an MTT tetrazolium reduction to formazan test, a colorimetric method to determine the number of viable cells, the 50% minimal lethal doses (CD50) for the siloxane compounds were found to range from 30 to 50 microM. Sublethal doses (e.g., 15 microM and lower) resulted in the loss of lactate dehydrogenase (LDH) and glutathione (GSH) from the cytosolic compartment of the target cells and thus indicated cytotoxicity. Treatment of macrophages with siloxanes resulted in a higher production of interleukin-6 (IL-6) than was exhibited by untreated macrophages. The B9 cell bioassay of these treated cells showed as much as a 10 fold higher production (500 U/ml) of IL-6 than did the untreated cells. The degree of increase was dependent on the compound and concentration used. The results of this study show that low molecular weight siloxanes produce lethal effects on B-lymphocyte derived target cells in vitro and permeabilize the plasma membranes at lower sublethal concentrations.
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PMID:Cytotoxicity and membrane damage in vitro by inclusion complexes between gamma-cyclodextrin and siloxanes. 856 93

The ability of dicatechol rooperol and esters to inhibit the production of cytokines in endotoxin-stimulated human alveolar macrophages, human blood monocyte/macrophages, histiocytic cell line U937, and rat alveolar macrophages was examined in vitro. Rooperol derivatives inhibited the production of tumour necrosis factor-alpha, interleukin-1 beta and interleukin-6. Of the esters tested on human cells, rooperol diacetate and tetraacetate were more potent inhibitors of cytokine production (IC50 in the range of 10-20 microM) than rooperol disulphate (IC50 in the range of 25-75 microM). The acetate esters also inhibited cytokine production in rat alveolar macrophages, whereas the sulphate had little effect. Rooperol and acetate esters, in the same concentration range, decreased the production of nitric oxide by rat alveolar macrophages stimulated by endotoxin. These concentrations of rooperol had no effect on cell viability, as indicated by incorporation of 14C-labelled leucine into macrophage proteins and their content of lactate dehydrogenase. The results obtained suggest that rooperol esters are potentially useful antiinflammatory agents.
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PMID:Cytokine production in human and rat macrophages and dicatechol rooperol and esters. 883 17


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