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)

Human interleukin-11 (IL-11) is a cytokine with a broad spectrum of activity, similar to interleukin-6 (IL-6). However, its role in human disease is poorly understood, partly because of a lack of sensitive bioassays. A subclone (B9-11) obtained from the B9 hybridoma (which responds poorly to human IL-11) enabled us to develop a highly sensitive bioassay for human IL-11. B9-11 cells responded only to human IL-11 and IL-6 and not to other human cytokines using the same gp130 transducer chain (ciliary neurotrophic factor, leukemia inhibitory factor and oncostatin M) or to other human interleukins (interleukin-1 to interleukin-13), human hematopoietic cytokines (granulocyte colony stimulating factor, granulocyte-macrophage colony stimulating factor, colony stimulating factor-1) and various other human cytokines (interferon-alpha, tumor necrosis factor-alpha, tumor necrosis factor-beta, fibroblast growth factor and nerve growth factor). In addition, these cytokines did not interfere with the IL-11 response of B9-11 cells. IL-11-induced proliferation of B9-11 cells was unaffected by anti-murine IL-6 receptor mAb but inhibited by anti-gp130 mAb. Half-maximal proliferation of B9-11 cells was obtained with 30 pg/ml of recombinant IL-11, a concentration 300-fold lower than IL-11 concentrations known to be active on human cells. Finally, culturing of B9-11 cells with an anti-IL-6 mAb enabled us to measure the natural IL-11 produced by various cell lines. Thus, B9-11 cells should be useful for studies of IL-11 involvement in various human diseases as well as for a better understanding of the mechanisms of action of this cytokine.
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PMID:A highly sensitive quantitative bioassay for human interleukin-11. 803 82

Prolactin (PRL) secretion and PRL mRNA expression in human myometrial explant cultures was inhibited by the addition of human placental conditioned medium (HPCM). After 3 days treatment with 5% HPCM PRL secretion was reduced to 24% of control values (P < 0.001). The effect persisted even after removal of progesterone, which suppresses myometrial PRL production, from the HPCM. In search for additional regulatory substances present in the uteroplacental unit, we tested a number of growth factors and cytokines known to affect pituitary PRL secretion. Treatment with endothelin-3 (ET-3) at a dose of 10(-6) M was found to increase PRL release by 20% over 3 days (P < 0.05) whereas interleukin-6 (IL-6) showed no effect on PRL levels. Epidermal growth factor, vasoactive intestinal peptide and interferon-alpha (IFN-alpha) were inhibitory. Interleukin-4 (IL-4) was the most potent inhibitor of PRL expression in myometrial tissue, causing a reduction of secreted PRL to less than 50% of controls after 3 days at a dose of > or = 5 ng/ml (P < 0.001) and a concomitant reduction of PRL mRNA levels. These results demonstrate a modulation of PRL expression in the myometrium by locally present factors.
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PMID:Modulation of prolactin secretion in human myometrium by cytokines. 804 33

Several peptides (cytokines), viz., interleukin-1 (IL-1), interferon-alpha (IFN-alpha), interleukin-6 (IL-6), tumor necrosis factor (TNF), are formed in response to conditions causing tissue inflammation or damage and are implicated in reactive changes of the host, including fever, while IL-1 has been considered an important mediator of fever, the other cytokines, specifically IL-6 and TNF, have recently acquired prominence. The present study extends earlier research on IL-1 and addresses the question of the role of IL-6 and TNF in the genesis of fever. Experiments were conducted in the conscious cat, and IL-6 and TNF were assayed concomitantly in cerebrospinal fluid (CSF) from the third ventricle using specific bioassays. In the absence of fever, IL-6 was usually below the threshold of the assay (4-32 pg/ml), while TNF appeared measurable (424 +/- 57 pg/ml) in most experiments. A single intravenous injection of endotoxin (bolus) or continuous infusion of IL-1 at doses eliciting a sustained fever increased CSF levels of IL-6, but had no effect on concentrations of TNF. Intracerebroventricular injection of a pyrogenic dose of endotoxin led to an elevation of TNF and IL-6 and, in either case, the effect was manifest during the latent period before the fever. In addition, by the same route, IL-1 caused a rise in IL-6. We conclude that brain is intrinsically capable of producing both IL-6 and TNF depending on the site of challenge. However, since IL-6 CSF levels are elevated regardless of the site of pyrogen injection, IL-6 lends itself better to a role in the pathogenesis of fever.
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PMID:Interleukin-6 and tumor necrosis factor in cerebrospinal fluid: changes during pyrogen fever. 833 Jan 97

In this study we evaluated the effect of recombinant interferon-alpha 2b (IFN-alpha 2b) therapy on the number of circulating platelets and interleukin-6 (IL-6) plasma levels in 12 human immunodeficiency virus type 1 (HIV-1) seropositive patients, affected by a severe and persistent thrombocytopenia. The levels of IL-6 in plasma of HIV-1 seropositive thrombocytopenic subjects before IFN-alpha therapy were similar (80 +/- 15 pg/ml) to those observed in 15 HIV-1 seropositive asymptomatic individuals (75 +/- 12 pg/ml) and 30 HIV-1 seronegative blood donors (59.5 +/- 25 pg/ml). On the other hand, IL-6 amounts (148 +/- 36 pg/ml) in plasma of HIV-1 seropositive thrombocytopenic subjects were significantly (p < 0.01) increased after 5 weeks of IFN-alpha 2b therapy, showing a good correlation (p < 0.05, chi-square test) with the levels of circulating platelets. Moreover, an increased spontaneous IL-6 production by peripheral blood monocytes was observed after IFN-alpha 2b therapy in HIV-1 seropositive thrombocytopenic patients. Our results suggest that an increased production of IL-6, one of the main factors controlling thrombocytopoiesis, may partially explain the ability of IFN-alpha 2b therapy, to restore platelet production in a subset of HIV-1 seropositive thrombocytopenic individuals.
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PMID:The elevation of circulating platelets after IFN-alpha therapy in HIV-1 seropositive thrombocytopenic patients correlates with increased plasma levels of IL-6. 846 69

To assess whether the initial status of lipid metabolism in patients with chronic viral hepatitis might correlate with outcome of therapy, 52 patients (32 males and 20 female) with chronic hepatitis C were studied: 44 were treated with human recombinant interferon-alpha 2b (3 MU three times per week for up to 12 months), and 8 served as controls. At baseline, sera were tested for total and HDL cholesterol, HDL2, HDL3, apolipoprotein A-I, apolipoprotein B, interferon-alpha, tumor necrosis factor, and interleukin-6. Changes in blood lipids were evaluated after 3, 30, and 90 days of treatment. HDL cholesterol, apolipoprotein A-I, and HDL3 decreased by 9.4-11.4% within 4 weeks of starting interferon treatment, but this effect was sustained only in patients with a primary response to interferon. On multivariate analysis, a primary response to interferon correlated with higher apolipoprotein A-I and lower (< 2.23 pg/ml) interleukin-6 levels (p < 0.005 for both). In contrast, a sustained response was significantly more common in patients with low (< or = 13.3 pg/ml) serum interferon-alpha and lower interleukin-6 at baseline but did not correlate with any of the blood lipids. Thus, in chronic hepatitis C, interferon treatment induces specific changes in blood lipids. The concentration of apolipoprotein A-I at baseline is a strong predictor of primary response to treatment, and the likelihood of sustained response seems to be reflected by lower cytokine activation.
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PMID:Changes in blood lipid composition and response to interferon treatment in chronic hepatitis C. 852 43

Systemic administration of human interferon-alpha stimulates the pituitary-adrenal axis in men, but the exact mechanism still remains to be established. The present study was undertaken to examine the hypothesis that interferon-alpha may alter the circulating concentrations of the cytokines which involve the activation of the pituitary-adrenal axis. Eleven patients with chronically active hepatitis C were treated with human lymphoblastoid interferon-alpha (IFN: 6 x 10(6) IU/day) and changes in plasma adrenocorticotropin (ACTH), serum cortisol and cytokine concentrations were observed on both the first and second days of the treatment. Subcutaneous administration of IFN significantly increased plasma ACTH and serum cortisol concentrations by 3 h after the injection. Serum interleukin-6 (IL-6) increased with the increase in circulating ACTH and cortisol. There was a significant correlation between serum cortisol and IL-6 concentrations at 3 h. In contrast, an increase in serum interleukin-1 beta was only observed in one case. On the second day of IFN treatment, simultaneous administration of 25 mg diclofenac sodium eliminated the IFN effects on circulating ACTH, cortisol and IL-6 concentrations. The present studies demonstrated that circulating IL-6 increases after systemic IFN administration, resulting in activation of the pituitary-adrenal axis.
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PMID:Increase in serum interleukin-6, plasma ACTH and serum cortisol levels after systemic interferon-alpha administration. 855 63

Immune factors such as autoimmunity have been implicated in the genesis of autism, a neurodevelopmental disorder. Since autoimmune response involves immune activation, the plasma levels of interferon-alpha (IFN-alpha), interferon-gamma (IFN-gamma), interleukin-12 (IL-12), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and soluble intercellular adhesion molecule-1 (sICAM-1) were measured in autistic patients and age-matched normal controls. The levels of IL-12 and IFN-gamma were significantly (P < or = 0.05) higher in patients as compared to controls. However, IFN-alpha, IL-6, TNF-alpha, and sICAM-1 levels did not significantly differ between the two groups. Because macrophage-derived IL-12 is known to selectively induce IFN-gamma in T helper type-1 (Th-1) cells, it is suggested that IL-12 and IFN-gamma increases may indicate antigenic stimulation of Th-1 cells pathogenetically linked to autoimmunity in autism.
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PMID:Plasma increase of interleukin-12 and interferon-gamma. Pathological significance in autism. 896 8

1. The influence of interferon-alpha (IFN alpha) on the clearances of theophylline (TH), antipyrine (AP) and hexobarbitone (HB) was studied in seven cancer patients given IFN alpha as their only treatment. In addition, IFN alpha effects on drug clearance were correlated with changes in serum inflammatory cytokines and acute phase proteins. 2. A 'baseline' study was performed by administering an oral drug 'cocktail' of TH (150 mg), AP (250 mg) and HB (250 mg) with saline injected simultaneously and again 24 h later. One week later, an 'acute' study was performed at the initiation of IFN alpha therapy, 3 x 10(6) units injected with the drug cocktail and again 24 h later. After 2 weeks of IFN alpha treatment three times per week, a 'chronic' study was performed with IFN alpha injected the day prior to, simultaneously with, as well as 24 h after the drug cocktail. 3. Plasma samples were collected over 48 h and the clearances of TH, AP and HB were estimated. Serum samples were collected at various times for the measurement of tumor necrosis factor (TNF), interleukin-1 (IL-1), interleukin-6 (IL-6), C-reactive protein (C-RP) and alpha 1-acid glycoprotein (AGP). 4. IFN alpha caused a 33% decrease in the oral clearance of TH during the chronic study compared with baseline (P < or = 0.05). Although IFN alpha inhibited TH clearance by 16% during the acute study and AP clearance by 20-21% during both acute and chronic studies, these changes did not reach statistical significance. IFN alpha caused minimal changes in HB clearance. There were no chronic effects of IFN alpha on serum cytokines or acute phase proteins. 5. The findings confirm that the most commonly used dose of IFN alpha inhibits the hepatic clearance in humans of some but not all drugs and that this inhibition persists during IFN alpha therapy. Because inhibition was not associated with increases in serum cytokines or acute phase proteins, the mechanism by which IFN alpha inhibits cytochrome P450 activities in vivo does not appear to involve inflammatory mediators such as TNF. IL-1 or IL-6.
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PMID:Effects of interferon-alpha monotherapy on hepatic drug metabolism in cancer patients. 911 9

Advances in molecular biology and recombinant DNA technology have led to the development of cytokines as therapeutic agents for a variety of disease states. The pharmacokinetic analysis of cytokines involves the understanding of analytical methods capable of detecting these agents in biological fluids and recognition of several factors which may have an impact on the cytokine concentration-time curves. Enzyme-linked immunosorbent assays (ELISA) have become the most common method of detection and commercial kits are available for a wide variety of cytokines. Monoclonal antibody products are sensitive, have minimal cross-reactivity and are relatively inexpensive when compared with high performance liquid chromatography (HPLC). However, the primary limitation of these assays is their inability to measure biologically active protein. Conversely, bioassays do measure a biological event (i.e. proliferation or cytotoxicity) but are generally not used for cytokine analysis because of their high cost, long assay completion time, lack of specificity, poor sensitivity and influence of environmental conditions on the outcome. The pharmacokinetic profile of recombinant cytokines is influenced by a number of variables: endogenous production, circulating soluble receptors and cell-associated receptors, immunocompetence and antibody production against the cytokine all may influence the disposition of the agent. Thus, pharmacokinetic modelling of cytokines may involve complex models capable of characterising these nonlinear processes and resulting effects. The route of administration is an important variable since cytokines administered by subcutaneous injection may be partially metabolised by proteases present in the subcutaneous tissue. Other methods to simplify cytokine delivery are being actively investigated and include formulations for inhalation, topical and oral administration. A variety of cytokines (including interferon-alpha, interleukin-6 and tumour necrosis factor) are capable of inhibiting cytochrome P450 hepatic enzymes and, therefore, possess the potential to cause drug-cytokine interactions. Inhibition has been demonstrated in several in vitro systems and animal models, although clinical data are currently limited. An increased understanding of the many factors which can alter the analysis and pharmacokinetics of cytokines is essential to the design of optimal dosage regimens.
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PMID:Pharmacokinetic studies with recombinant cytokines. Scientific issues and practical considerations. 916 Jan 71

The cytolytic and anti-proliferative effects of bacillus Calmette-Guerin (BCG) and/or interferon-alpha-2b (IFN-alpha-2b) on 5 human bladder carcinoma cell lines, RT4, RT112, MGH, SD and J82, were determined. The cell lines showed different sensitivities to BCG and IFN-alpha-2b. BCG had direct dose-dependent cytolytic and anti-proliferative effects on MGH, J82 and SD (grade 3 cell lines), whereas RT4 and RT112 (grades 1 and 2, respectively) were less sensitive. Surprisingly, higher concentrations of BCG enhanced cell growth of RT4. IFN-alpha-2b also had cytolytic and anti-proliferative effects on all 5 cell lines. Thus, the RT4 and RT112 cell lines that were not sensitive to BCG were highly sensitive to IFN-alpha-2b. A combination of BCG and IFN-alpha-2b had additive anti-proliferative effects on MGH, J82 and RT112. Interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) production by these 5 cell lines was measured after stimulation with BCG and/or IFN-alpha-2b, by ELISA immunoassays. Production of IL-6 and TNF-alpha was significantly increased in MGH and J82 cell lines by the combination of BCG and IFN alpha-2b. The enhanced cytolytic and anti-proliferative effects of the combination of BCG and IFN-alpha-2b may be related to the induction of cytokines.
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PMID:Effects of bacillus Calmette-Guerin and interferon-alpha-2B on human bladder cancer in vitro. 918 Jan 56


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