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)

Kaposi's sarcoma is a multifocal lesion that is reported to be greatly influenced by cytokines such as interleukin-6 (IL-6) and oncostatin M. DNA sequences of a novel human gammaherpesvirus, termed human herpesvirus 8 (HHV-8) or Kaposi sarcoma-associated herpesvirus, have been identified in all epidemiological forms of Kaposi's sarcoma with high frequency. The presence of HHV-8 DNA is also clearly associated with certain B-cell lymphomas (body cavity-based lymphomas) and multicentric Castleman's disease. Sequence analysis of a 17-kb fragment revealed that adjacent to a block of conserved herpesvirus genes (major DNA-binding protein, glycoprotein B, and DNA polymerase), the genome of HHV-8 encodes structural homolog of IL-6. This cytokine is involved not only in the pathogenesis of Kaposi's sarcoma but also in certain B-cell lymphomas and multicentric Castleman's disease. The viral counterpart of IL-6 (vIL-6) has conserved important features such as cysteine residues involved in disulfide bridging or an amino-terminal signal peptide. Most notably, the region known to be involved in receptor binding is highly conserved in vIL-6. This conservation of essential features and the remarkable overlap between diseases associated with HHV-8 and diseases associated with IL-6 disregulation clearly suggest that vIL-6 is involved in HHV-8 pathogenesis.
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PMID:Human herpesvirus 8 encodes a homolog of interleukin-6. 898 27

The hepatic capacity for acute phase protein synthesis after partial hepatectomy in the elderly patients was prospectively studied. Forty-one patients who consecutively underwent a partial hepatectomy were grouped according to age of greater or less than 70 years; 12 were in the older group and 29 in the younger. The changes in the levels of serum interleukin-6, alpha 1-antitrypsin, alpha 1-acid glycoprotein, haptoglobin, and plasma fibrinogen were measured after surgery. The postoperative changes in standard liver function tests were also measured. The incidence of postoperative infected complications was 25% in the older group and 7% in the younger (P = 0.28). Although postoperative levels of serum interleukin-6 were similar between the two groups, those of serum alpha 1-antitrypsin, alpha 1-acid glycoprotein, and haptoglobin were significantly lower in the elderly (P < 0.05). Postoperative levels of serum alpha 1-antitrypsin and plasma fibrinogen showed an increase of about 30% compared with the preoperative values (P < 0.05) in the younger group, but no significant increase in the older. Postoperative deterioration of serum albumin levels and hepaplastin test values was also significantly more severe in the older group (P < 0.05). We conclude that in the older patients, a reduction of acute phase protein synthesis occurs after partial hepatectomy as a result of a global deterioration of liver function, and may render patients liable to infection.
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PMID:Reduction of hepatic acute phase response after partial hepatectomy in elderly patients. 901 Sep 60

The purpose of this prospective study was to correlate measures of the acute phase response, associated therapeutic interventions, and other clinical variables with the process of altered drug metabolism previously observed in patients with severe neurotrauma. Nine patients with severe head injury (Glasgow Coma Scale < or = 8) requiring intravenous phenytoin were included in the study. A loading dose of phenytoin was followed by daily maintenance doses. Serial blood samples were taken after the loading dose and every even-numbered study day for 10 to 14 days for measurement of total and unbound concentrations of phenytoin, interleukin-1 beta, interleukin-6 (IL-6), tumor necrosis factor alpha, alpha 1-acid-glycoprotein, C-reactive protein, and albumin. Time-invariant and time-variant Michaelis-Menten models were fit to the phenytoin concentration-time data. Protein intake was closely monitored. The mean (+/- SEM) unbound fraction of phenytoin increased from 0.17 +/- 0.02 on day 1 to 0.24 +/- 0.04 on day 10 (P < 0.05). The time-variant model was superior in describing the concentration-time data of unbound phenytoin in eight of nine patients. Mean (+/- SEM) pharmacokinetic parameter estimates for unbound phenytoin were: Vmax delta = 605 +/- 92 mg/day, VmaxB = 149 +/- 26.3 mg/day, K(ind) = 0.013 +/- 0.004 hr-1. Interleukin-6 was the only cytokine with significant concentration changes over time; it was inversely correlated with Vmax,t. Peak concentrations of interleukin-6 also proved to be inversely correlated with VmaxB. The daily amount of protein administered was significantly correlated with Vmax,t. Significant alterations in the metabolism of phenytoin occur after severe neurotrauma. The etiology of these changes is probably multifaceted. These results suggest that low initial phenytoin Vmax may be explained by the presence of interleukin-6. An increase in oxidative metabolism that correlated with nutritional protein administration was observed later in these patients.
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PMID:Effect of acute phase response on phenytoin metabolism in neurotrauma patients. 905 39

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

Based on previous studies we hypothesized that interleukin-6 (IL-6) plasma levels would increase during the menstrual cycle, in analogy to the increase in IL-1 levels seen during the luteal phase. Thus we have investigated menstrual cycle-associated changes in IL-6, alpha1 acid glycoprotein (AGP), and C-reactive protein (CRP). The study design was cross-sectional and was conducted in 18 healthy premenopausal women with regular menstrual cycles and in 15 age-matched men. The women had blood drawings in the follicular phase, at midcycle, and in the luteal phase of the menstrual cycle. A single blood sample was obtained from men to compare IL-6 levels between sexes. The median IL-6 level was 0.68 pg/ml (95% confidence interval (CI): 0.60 to 1.05) in the follicular phase and did not change significantly during the menstrual cycle. IL-6 levels did not differ between women and men (0.79 pg/ml; CI: 0.66 to 1.05; p > 0.05). Median AGP levels decreased by 6% (CI: -14% to 1%) during the luteal phase (p = 0.005), and a significant correlation between mean AGP and IL-6 levels was found (r = 0.60; p = 0.01). Median CRP levels increased by 44% (CI: 27% to 59%; p < 0.001) at midcycle and by 31% (CI: 17% to 68%; p = 0.002) in the luteal phase, and there was a significant correlation between the relative increase in CRP at midcycle and the relative increase in progesterone levels during midcycle (r = 0.60; p = 0.01) and the luteal phase (r = 0.71; p = 0.001). In conclusion, we found no sustained menstrual cycle-dependent changes in systemic IL-6 plasma levels. AGP and CRP levels may be differentially regulated during the menstrual cycle of healthy women: AGP levels correlated with IL-6 levels, and AGP levels decreased during the menstrual cycle, whereas CRP levels increased during the menstrual cycle and correlated with the increase in progesterone levels. The reason for the observed changes in CRP levels remains to be elucidated.
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PMID:Menstrual cycle-associated changes in blood levels of interleukin-6, alpha1 acid glycoprotein, and C-reactive protein. 924 68

In order to get a better insight into cytokine network regulation in systemic lupus erythematosus (SLE), we analyzed levels of interleukin-10 (IL-10), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma) in the sera from 36 SLE patients. Moreover, C-reactive protein (CRP), alpha-1-acid-glycoprotein (AGP), and alpha-1-antichymotripsin (ACT) serum levels were evaluated. Serum levels of IL-10 and IL-6 were significantly increased when compared with healthy controls. TNF-alpha and IFN-gamma did not differ from normal values. We established the relationship between IL-10 and IL-6 as well as between IL-10 and TNF-alpha. None of the analyzed cytokines correlated with the acute phase protein levels. Based on the obtained data, we conclude that IL-10 may play the superior regulating role in SLE. A lack of correlation between the cytokines and acute phase proteins suggests their independence from cytokine regulation.
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PMID:Cytokine concentration in serum of lupus erythematosus patients: the effect on acute phase response. 924 16

The membrane-bound gp130 glycoprotein acts as an affinity converting and signal transducing receptor (R) for interleukin-6 and several other cytokines. In this work, we RT-PCR amplified gp130 cDNA using primers flanking the sequence encoding the transmembrane domain of gp130. We observed in blood mononuclear cells, in addition to the expected 333-bp length fragment, a second major band of 418 bp. Sequencing of the 418-bp fragment and its genomic counterpart showed a new 85-bp exon located in the sequence encoding the extracellular region of the gp130 protein. This exon is most likely due to alternative splicing and leads to a frame-shift resulting in a stop-codon 1 bp before the transmembrane coding region. Correspondingly, supernatants from chinese hamster ovary cells transfected with this cDNA contained 4-5 times more soluble (s) gp130 than supernatants from cells transfected with a cDNA encoding the membrane-bound gp130 protein. Both gp130 and alternatively spliced sgp130 were also transcribed by the myeloma cell lines XG-1, XG-2, XG-4, XG-4CNTF XG-6, XG-7, XG-9, XG-10, U266 and RPMI 8226. However, XG-4A cells derived from XG-4 cells, but growing independently of exogenous IL-6, did not transcribe sgp130 mRNA. A possible interference with intracrine stimulatory factors by alternatively spliced sgp130 needs to be further investigated.
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PMID:Cloning and expression of an alternatively spliced mRNA encoding a soluble form of the human interleukin-6 signal transducer gp130. 925 56

A herpesvirus that is related to but distinct from the Kaposi's sarcoma-associated herpesvirus (KSHV, or human herpesvirus 8) was isolated from rhesus monkeys. The sequence of 10.6 kbp from virion DNA revealed the presence of an interleukin-6 homolog similar to what is present in KSHV and a closer relatedness of the DNA polymerase and glycoprotein B reading frames to those of KSHV than to those of any other herpesvirus. This rhesus monkey herpesvirus replicated lytically and to high titers in cultured rhesus monkey fibroblasts. Antibody testing revealed a high prevalence for at least 10 years in our rhesus monkey colony and a high prevalence in two other colonies that were tested. Thus, rhesus monkeys naturally harbor a virus related to KSHV, which we have called RRV, for rhesus monkey rhadinovirus.
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PMID:A herpesvirus of rhesus monkeys related to the human Kaposi's sarcoma-associated herpesvirus. 937 42

Non-insulin-dependent diabetes mellitus (NIDDM) is commonly associated with hypertriglyceridaemia, low serum HDL-cholesterol concentrations, hypertension, obesity and accelerated atherosclerosis (metabolic syndrome X). Since a similar dyslipidaemia occurs with the acute-phase response, we investigated whether elevated acute-phase/stress reactants (the innate immune system's response to environmental stress) and their major cytokine mediator (interleukin-6, IL-6) are associated with NIDDM and syndrome X, and may thus provide a unifying pathophysiological mechanism for these conditions. Two groups of Caucasian subjects with NIDDM were studied. Those with any 4 or 5 features of syndrome X (n = 19) were compared with a group with 0 or 1 feature of syndrome X (n = 25) but similar age, sex distribution, diabetes duration, glycaemic control and diabetes treatment. Healthy non-diabetic subjects of comparable age and sex acted as controls. Overnight urinary albumin excretion rate, a risk factor for cardiovascular disease, was also assayed in subjects to assess its relationship to the acute-phase response. Serum sialic acid was confirmed as a marker of the acute-phase response since serum concentrations were significantly related to established acute-phase proteins such as alpha-1 acid glycoprotein (r = 0.82, p < 0.0001). There was a significant graded increase of serum sialic acid, alpha-1 acid glycoprotein, IL-6 and urinary albumin excretion rate amongst the three groups, with the lowest levels in non-diabetic subjects, intermediate levels in NIDDM patients without syndrome X and highest levels in NIDDM patients with syndrome X. C-reactive protein and cortisol levels were also higher in syndrome X-positive compared to X-negative patients and serum amyloid A was higher in both diabetic groups than in the control group. We conclude that NIDDM is associated with an elevated acute-phase response, particularly in those with features of syndrome X. Abnormalities of the innate immune system may be a contributor to the hypertriglyceridaemia, low HDL cholesterol, hypertension, glucose intolerance, insulin resistance and accelerated atherosclerosis of NIDDM. Microalbuminuria may be a component of the acute-phase response.
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PMID:NIDDM as a disease of the innate immune system: association of acute-phase reactants and interleukin-6 with metabolic syndrome X. 2212 8

Many attempts have been made over recent years to assess accurately disease activity in Crohn's disease. We review some of these attempts, giving particular emphasis to the combination of serum levels of proinflammatory cytokines (interleukin-6, tumour necrosis factor alpha, recombinant interleukin-2 and acid alpha-1-glycoprotein).
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PMID:Assessing disease activity in Crohn's disease--are we there yet? 939 81


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