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)

1. Leukocyte enumeration through flow cytometry has revealed that severe depression may be accompanied by a systemic immune activation, indicative of an inflammatory response. The latter condition allegedly involves an important modification of acute phase plasma protein (APP) equilibrium. 2. In order to elucidate whether the state of severe depression is represented by alterations in APPs, the authors measured: alpha 1 antitrypsin (alpha 1 AT), alpha 2 macroglobulin (alpha 2 M), haptoglobin (Hp), alpha 1 acid glycoprotein (alpha 1 S), transferrin (Tf), complement component 4 (C4) and C-reactive protein (CRP). Interleukin-1-beta (II-1 beta) and interleukin-6 (II-6) circulating levels were determined. 3. Hyperhaptoglobinemia and hypotransferrinemia are hallmarks for major depression and depression per se, respectively. The disorders in Hp and Tf circulating levels are highly sensitive to (83%) and specific for (100%) melancholia as opposed to the healthy state. 4. Disorders in both APPs are significantly related to the absolute number of blood monocytes. 5. The authors observed a trend towards lower alpha 2M and higher alpha 1S values in severely depressed subjects. Severity of depression was significantly related to Hp and alpha 1S (both positively) and to alpha 2M and Tf (both negatively) values. 6. No significant intercategory differences in C4 could be established, whilst only a few subjects exhibited measurable CRP, II-1 beta and II-6 circulating levels. 7. Our findings may support the hypothesis that depression is accompanied by an inflammatory response.
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PMID:Disturbances in acute phase plasma proteins during melancholia: additional evidence for the presence of an inflammatory process during that illness. 137 70

The serum level of rat alpha 1-acid glycoprotein is significantly increased by treatment with phenobarbital, and in vivo studies have shown that phenobarbital seems to act mainly at the transcriptional level. To show the direct mediating effect of phenobarbital on alpha 1-acid glycoprotein gene expression, we investigated the ability of primary cultured rat hepatocytes to respond to in vitro phenobarbital administration. Phenobarbital increased both alpha 1 acid glycoprotein secretion and corresponding mRNA levels in primary rat hepatocytes cultured on matrigel. Used in combination with interleukin-1, interleukin-6 and dexamethasone, phenobarbital had an additive or synergistic effect on alpha 1-acid glycoprotein synthesis. These results show that (a) phenobarbital acts directly on hepatocytes by increasing alpha 1-acid glycoprotein gene expression and (b) this effect is mediated by a specific mechanism independent of pathways involved in alpha 1-acid glycoprotein induction by interleukin-1, interleukin-6 and glucocorticoids.
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PMID:Phenobarbital induction of alpha 1-acid glycoprotein in primary rat hepatocyte cultures. 798 58

Cardiotrophin-1 (CT-1) is a recently isolated cytokine belonging to the interleukin-6 cytokine family. In the present study, we show that CT-1 binds to hepatocyte-derived cell lines of rat and human origin with high (Kd = 600-800 pM) and low (Kd approximately 3-6 nM) binding affinities. Treatment of HepG2 cells with CT-1 resulted in the induction of tyrosine phosphorylation of both transducing receptor subunits, gp130 and LIF receptor, and this phosphorylation was completely inhibited by a neutralizing anti-gp130 mAb. Addition of CT-1 to HepG2 or H35 cell cultures induced a dose-dependent production of several acute phase proteins (haptoglobin, fibrinogen, alpha1-acid glycoprotein, alpha2-macroglobulin). Moreover, the use of a neutralizing mAb to gp130 in cultures of HepG2 cells grown in the presence of CT-1, inhibited the induction of acute phase protein secretion, indicating an absolute requirement of gp130 in the formation of a functional CT-1 receptor. Altogether, these results suggest that CT-1 could play an important role in the regulation of hepatocyte metabolism in inflammatory responses.
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PMID:Hepatocyte-derived cell lines express a functional receptor for cardiotrophin-1. 934 56

The acute-phase protein (APP) response is regulated by cytokines such as interleukin-6 (IL-6), interleukin-1 (IL-1) and tumor necrosis factor (TNF), but may also be influenced by malnutrition. The aims of this study were as follows: 1) to determine in rats the effect of a protein-deficient diet on IL-6 mRNA expression in intestine, liver and peripheral blood mononuclear cells (PBMC), and on alpha-1 acid glycoprotein (AGP) and alpha-2 macroglobulin (A2M) serum levels and hepatic mRNA expression; 2) to compare, in protein-deficient rats, the IL-6 and APP responses after a turpentine (TO)- or a lipopolysaccharide (LPS)-induced inflammation; and 3) to determine the effect of a protein malnutrition on IL-6 mRNA expression in rat PBMC treated ex vivo with LPS. Interleukin-6 mRNA was present in intestine and PBMC but not in the liver of malnourished rats, and was absent in any tissue or cells of controls. A2M was present in the serum from malnourished rats but not after refeeding. AGP mRNA expression was not influenced by protein malnutrition. In malnourished rats, IL-6 serum level peaked later than in controls after TO and LPS treatment. In malnourished TO-treated rats, A2M mRNA increased earlier than in controls and remained detectable later than in controls. AGP mRNA expression after TO was not influenced by protein malnutrition. In PBMC of malnourished rats, LPS-induced IL-6 mRNA expression occurred earlier and lasted longer than in controls. Our results indicate that protein malnutrition by itself induces IL-6 and A2M expression, and that it modulates the APP response to inflammation.
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PMID:Induction and modulation of acute-phase response by protein malnutrition in rats: comparative effect of systemic and localized inflammation on interleukin-6 and acute-phase protein synthesis. 944 38

The ODS rat (genotype od/od), which has a hereditary defect in ascorbic acid biosynthesis, was used to investigate the effects of ascorbic acid deficiency on the hepatic gene expression of both the positive acute phase proteins, haptoglobin and alpha1-acid glycoprotein, and the negative acute phase proteins, apolipoprotein A-I and albumin. Male ODS rats (6 wk old, body weight approximately 140 g) were fed a basal diet containing ascorbic acid (300 mg/kg diet) or a diet without ascorbic acid for 14 d. Ascorbic acid deficiency significantly elevated the serum concentration of haptoglobin and significantly lowered those of apolipoprotein A-I and albumin. The hepatic mRNA levels of haptoglobin and alpha1-acid glycoprotein in the ascorbic acid-deficient rats were significantly elevated on d 12, and reached 260 (P < 0.05) and 360% (P < 0.01) of respective values in the control rats on d 14. On the contrary, the hepatic mRNA levels of apolipoprotein A-I and albumin in the ascorbic acid-deficient rats were lowered to 68 (P < 0.01) and 71% (P < 0.05) of respective values in the control rats on d 14. Although ascorbic acid deficiency significantly elevated the serum corticosterone concentration on d 14, the changes in mRNA levels of haptoglobin, alpha1-acid glycoprotein, apolipoprotein A-I and albumin due to ascorbic acid deficiency were not affected by adrenalectomy, as assessed in a separate experiment. The serum concentration of interleukin-6, an inflammatory cytokine that stimulates gene expression of some acute phase proteins, was significantly higher in the ascorbic acid-deficient rats on d 14 than in the control rats. These results suggest that ascorbic acid deficiency causes physiologic changes similar to those that occur in the acute phase response.
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PMID:Ascorbic acid deficiency changes hepatic gene expression of acute phase proteins in scurvy-prone ODS rats. 956 89

The concentration of interleukin-6 (IL-6), alpha1-acid glycoprotein (alpha1-AG), and corticosterone (CORT) was investigated chronologically (0 h to 14 d) in the sera of 2-wk-old specific-pathogen-free chicks inoculated with Escherichia coli lipopolysaccharide (LPS). In the LPS group the IL-6 level was elevated from 1 h to 2 d and was the highest at 3 h. From 4 to 14 d the IL-6 level was low in the LPS group. In the PBS group, IL-6 was not detected except a mild increase from 1 h to 6 h. In the LPS group, the alpha1-AG level increased from 6 h to 4 d, and the peak was 2 d. In the PBS group the alpha1-AG level was always low. The CORT level in the LPS group was higher than that of PBS group at 1 h. This study suggests that E. coli LPS may elevate serum IL-6 and CORT, and that IL-6 and CORT may increase the alpha1-AG level in the chicks.
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PMID:Serum levels of interleukin-6, alpha1-acid glycoprotein, and corticosterone in two-week-old chickens inoculated with Escherichia coli lipopolysaccharide. 962 44

1. This study investigates whether previously documented effects of interleukin-4 in down-regulating pro-inflammatory cytokine production by peripheral blood mononuclear cells (PBMCs) from healthy individuals would be reproducible in PBMCs isolated from patients with multiple organ failure (acute disease model) and gastrointestinal cancer (chronic disease model). The effects of interleukin-4 on the ability of PBMC supernatants to elicit an acute phase protein response from isolated human hepatocytes were also studied. 2. Incubation of PBMCs with interleukin-4 significantly reduced both spontaneous and lipopolysaccharide-induced production of tumour necrosis factor and lipopolysaccharide-induced interleukin-6 production, demonstrating that the PBMCs from patients with acute and chronic disease are not refractory to the effects of interleukin-4. The effects of interleukin-4 on the ability of PBMCs from the groups studied to elicit an acute phase response were complex and varied both between patient groups and individual acute phase proteins. Overall, interleukin-4 reduced the potential of PBMCs to stimulate production of the positive acute phase proteins C-reactive protein, alpha1-antichymotrypsin and alpha1-acid glycoprotein.3. This work emphasizes the pleiotropic nature of cytokines and the complex regulatory mechanisms which exist. The study illustrates the difficulties in devising in vivo intervention strategies using cytokines such as interleukin-4.
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PMID:Effect of interleukin-4 on pro-inflammatory cytokine production and the acute phase response in healthy individuals and in patients with cancer or multiple organ failure. 973 Aug 55

Oncostatin M (OSM) is an interleukin-6 (IL-6) family cytokine known in particular to induce the synthesis of acute-phase proteins by hepatocytes. Because human polymorphonuclear neutrophils (PMN) can secrete numerous cytokines, the potential production of OSM by PMN was investigated. Highly purified PMN were found to contain an intracellular stock of preformed OSM that was rapidly mobilized by degranulating agents such as phorbol myristate acetate and granulocyte-macrophage colony-stimulating factor (GM-CSF). Moreover, PMN produced OSM after a few hours of stimulation by various agonists. The most potent effect was observed with the combination of lipopolysaccharide and GM-CSF, which had a concentration- and time-dependent effect at both the protein and mRNA levels. Actinomycin D strongly reduced OSM mRNA induction, suggesting the involvement of gene transcription. Cycloheximide inhibited OSM protein synthesis but did not affect the release of preformed stores. In addition, OSM production was downregulated by dexamethasone, whereas IL-10 had no effect. The OSM produced by PMN was biologically active, as demonstrated by its ability to induce alpha1-acid glycoprotein synthesis by HepG2 cells. OSM secretion thus occurs through a two-step mechanism in PMN, consisting of early release of a preformed stock, followed by de novo protein synthesis. This would allow rapid and sustained OSM release to occur at inflammatory sites, and may contribute to the modulation of local inflammation.
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PMID:Oncostatin M production and regulation by human polymorphonuclear neutrophils. 994 86

Activin, and its binding protein, follistatin, are up-regulated by mediators of inflammation, and recent studies have demonstrated that activin A can block the activity of the key inflammatory cytokine, interleukin-6 (IL-6). These findings thereby implicate activin and follistatin in the control of the inflammatory cascade. In this study, interactions between interleukin-1beta (IL-1beta), IL-6 and activin were examined the human liver cell line, HepG2, for their effect on cell proliferation and the production of the acute phase proteins, haptoglobin and alpha1-acid glycoprotein (alpha1-AGP). IL-1beta and activin A, but not IL-6, inhibited the proliferation of HepG2 cells. Activin A together with IL-1beta caused a greater inhibition of proliferation than either factor alone, and the inhibitory effects of activin A were blocked by the addition of follistatin to the cultures. Activin A alone inhibited the production of haptoglobin but did not affect alpha1-AGP concentrations. However, activin A suppressed the stimulatory effects of IL-6 on the production of both haptoglobin and alpha1-AGP. Production of follistatin by HepG2 cells was stimulated by activin A, but was inhibited by both IL-1beta and IL-6, indicating a complex regulatory loop is operable to modulate the effects of activin A during inflammation. Taken together, these data suggest that activin A interacts with IL-1beta and IL-6 to regulate and coordinate the production of acute phase proteins during an inflammatory episode.
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PMID:Activin A regulates growth and acute phase proteins in the human liver cell line, HepG2. 1022 78

Inflammatory phenomena at sites of atherosclerotic plaques are increasingly thought to be major determinants of the progression and clinical outcome of atherosclerotic disease. Therefore, attention is being paid to systemic markers/mediators which may reflect the inflammatory activity in the plaques. This study evaluates the pattern of the main proinflammatory cytokines tumor necrosis factor-alpha (TNFalpha), interleukin-1beta (IL-1beta), and interleukin-6 (IL-6), their soluble receptors/antagonist, and a variety of inflammatory markers, in patients with peripheral arterial disease (PAD). Eight patients with PAD suffering from claudicatio intermittens (CI), eight with critical limb ischemia (CLI) and eight controls (C) were studied. Blood samples were collected at baseline in all groups and. for C and CI, immediately after and 4 h after a 30-min treadmill test. Baseline: no differences in cytokine plasma levels were detected among the three groups. In contrast, soluble receptors of TNF (type I and II) and of IL-6, and IL-1beta receptor antagonist (IL-1ra) were increased in CI and CLI patients, as compared to C. Of note, IL-Ira correlated with the occurrence and stage of the disease in a highly significant proportion of the patients, reaching a predictive value for the disease of P < 0.0001. The opposite trend was observed for the soluble receptor of IL-1beta. Notably, in the patients no alterations could be found in white blood cell counts, expression of CD11c adherence molecule by circulating monocytes or, in vitro. O2- release from zymosan-activated neutrophils. Moreover, plasma levels of platelet activating factor (PAF), of neutrophil elastase and of the acute phase reactants C-reactive protein (CRP) and alpha1-acid glycoprotein were not found to be significantly altered. In contrast, the acute-phase proteins alpha1-antitrypsin (alpha1AT) and haptoglobin (HG) were found to be increased. Effect of treadmill: IL-1beta and TNFalpha remained at baseline levels following exercise, and IL-6 dropped to undetectable levels. Among cytokine antagonists, again the most relevant changes concerned the IL-1ra, which was significantly increased immediately after the treadmill test, both in CI and C, and returned to baseline levels after 4 h. In contrast, soluble TNFalpha, IL-1beta and IL-6 receptors, PAF, and the other markers of leukocyte activation were not found to be altered. Soluble TNFalpha and IL-6 receptors were shown to inhibit the biological effects of their ligands. Similarly, IL-1ra and the acute phase proteins alpha1AT and HG have been reported to exert anti-inflammatory functions. The increased plasma levels of these agents, together with low levels of inflammatory cytokines and other pro-inflammatory mediators such as PAF and alpha1-acid glycoprotein, appear to draw an undescribed picture, so far, of upregulation of a composite systemic anti-inflammatory mechanism in atherosclerotic patients. IL-1ra appears to be a reliable marker of the state of activation of this mechanism. These results may provide a basis for developing new insights into the pathogenesis of the atherosclerotic disease.
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PMID:Atherosclerosis and inflammation. Patterns of cytokine regulation in patients with peripheral arterial disease. 1042 95


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