UNIPROT:P05231 - FACTA Search

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Query: UNIPROT:P05231 (interleukin-6)
23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human hepatoma cell line, HepG2, has been infected with vaccinia virus and synthesis of plasma proteins was determined by electroimmunoassay and corresponding mRNA's measured by Northern blotting. The inhibitory effect of the virus was dose- and time-dependent. Electrophoretic mobility shift assay revealed a decrease in C/EBP binding activities in nuclear extracts isolated from the infected hepatoma cells. Supershift analysis of the C/EBP isoforms showed alpha and beta subunit involvement in DNA binding. The treatment of the cells with interleukin-1, interleukin-6, and dexamethasone at the initial stage of infection appears to delay the virally induced inhibition of host cell protein synthesis. Thus, possible "protective" role of the acute phase cytokines in viral infection is proposed.
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PMID:Vaccinia virus-induced changes in cytokine-regulated acute phase plasma protein synthesis by hepatoma cells. 962 62

The pineal neurohormone melatonin functionally synchronizes the organism with the photoperiod. It is now well recognized that melatonin also plays an important immunoregulatory role. T-helper cells bear G-protein coupled melatonin cell-membrane receptors and, perhaps, melatonin nuclear receptors. Activation of melatonin receptors enhances the release of T-helper cell type 1 (Th1) cytokines, such as gamma-interferon and interleukin-2, as well as of novel opioid cytokines which crossreact immunologically with both interleukin-4 and dynorphin B. Melatonin has also been reported to enhance the production of interleukin-6 from human monocytes. These mediators may counteract secondary immunodeficiencies, protect mice against lethal viral and bacterial diseases, synergize with interleukin-2 in cancer patients and influence hematopoiesis. Hematopoiesis is apparently influenced by the action of the melatonin-induced opioids on kappa-opioid receptors present on stromal bone marrow cells. Most interestingly, gamma-interferon and colony stimulating factors may modulate the production of melatonin in the pineal gland. A hypothetical pineal-immune-hematopoietic network is, therefore, taking shape. From the immunopharmacological point of view, a call is made for clinical studies on the effect of melatonin in viral disease including human immunodeficiency virus-infected patients and cancer patients. In conclusion, melatonin seems to be an important immunomodulatory hormone which deserves to be further studied to identify its relevance in immune-based diseases, its therapeutic indications, and its adverse effects.
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PMID:The photoperiod transducer melatonin and the immune-hematopoietic system. 971 19

Interleukin-6 (IL-6) is a pleotropic cytokine implicated in the pathogenesis of local inflammation during viral upper respiratory infections. This study determined if experimental influenza A virus infection causes local IL-6 production. Seventeen healthy, adult subjects were intranasally inoculated, by course drops, with a safety-tested strain of influenza A/Kawasaki/86 (H1N1) virus. Nasal lavage samples were collected, symptoms were recorded, and expelled nasal secretions were weighed once before and then daily for 8 days after the virus inoculation. Lavage samples were submitted for virus culture and were examined for IL-6 and IL-4 by enzyme-linked immunosorbent assay. The IL-6, but not IL-4, levels were significantly increased in the nasal lavage samples of the 12 subjects who shed virus but not in those of the 5 subjects who did not shed virus. Moreover, the elevations in IL-6 levels were related temporally to the development of nasal symptoms and secretions but not to systemic symptoms. These results suggest a role for locally produced IL-6 in the pathogenesis and expressed symptomatology of influenza A virus infection.
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PMID:Increased interleukin-6 levels in nasal lavage samples following experimental influenza A virus infection. 972 23

Cytokines are soluble polypeptides with many physiological functions and a special role during infection and inflammation. Little is known about cytokine regulation in naturally occurring viral diseases of animals. Especially the role of cytokines in the development and progression of lesions in canine distemper virus (CDV) infection in dogs is largely unknown. Whole blood samples from 14 dogs with CDV infection and three dogs suffering from non-distemper diseases were examined for mRNA of pro-inflammatory cytokines such as interleukin-1beta (IL-1), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-12 (IL-12), tumor necrosis factor-alpha (TNF), interferon-gamma (IFN), and the anti-inflammatory transforming growth factor-beta1 (TGF) using reverse transcription polymerase chain reaction (RT-PCR). Blood samples from the three dogs that showed no clinical abnormalities during a pre-vaccination physical examination served as control. CDV infection was confirmed by post-mortem immunohistochemistry for CDV nucleoprotein. The degree of immunoreactivity and the number of virus antigen positive organs were expressed as antigen index. IFN transcripts were not identified in any dog and IL-8 transcripts were present in RNA isolates from all 20 dogs. None of the other cytokines was detected in control animals. IL-1 and IL-6 were each found in one non-distemper dog and TGF transcripts were amplified in two dogs with non-distemper disease. The following transcripts were found in variable numbers in distemper dogs: IL-1 (7/14 dogs), IL-6 (3/14 dogs), IL-12 (3/14 dogs), TNF (8/14 dogs), and TGF (10/14 dogs) with multiple cytokines in ten dogs. No cytokine transcripts were detected in three distemper dogs. There was no obvious correlation between cytokine mRNA expression and respiratory and gastrointestinal tract diseases. In the CNS, demyelination was frequently associated with IL-1, IL-12, TNF and TGF mRNA expression in the blood. IL-6 transcripts were found only in animals with early CNS lesions and TGF was the only detectable cytokine in an animal with chronic demyelination. Lack of detectable cytokine transcripts in whole blood samples was associated with a high antigen index and viremia, indicating that an overwhelming virus infection may suppress cytokine production, possibly due to paralysis of the immune system. Simultaneous occurrence of pro- and anti-inflammatory cytokines in whole blood preparation from most of the dogs with distemper, indicated a complex most likely disease stage dependent orchestrated cytokine expression.
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PMID:Cytokine mRNA expression in whole blood samples from dogs with natural canine distemper virus infection. 980 73

Bovine herpesvirus type 1 (BHV-1) glycoprotein D (gD) engenders mucosal and systemic immunity and protects cattle from viral infection. Chimerization of cytokines with gD is being explored to confer intrinsic adjuvanticity on gD. Addition of the appropriate cytokine may convert gD into an antigen that specifically engenders protective mucosal immunity. Here DNA coding for the mature bovine interleukin-6 (IL-6) protein was fused through a synthetic glycine linker to the 3' end of DNA coding for the mature BHV-1 gD (tgD) external domain. It was cloned behind the yeast alpha prepro signal sequence and transfected into Pichia pastoris which secreted the chimeric protein (tgD-IL-6) as a 100 kDa molecule. This chimera combined the immunogenic properties of native gD and the in vitro biological activity of bovine IL-6 based on the following observations. A panel of BHV-1 gD-specific monoclonal antibodies recognizing five neutralizing epitopes on native gD reacted with tgD-IL-6. Sera from yeast tgD-IL-6-immunized mice neutralized BHV-1 infection in vitro. The chimeric protein enhanced total bovine immunoglobulin production 16-fold above tgD alone in pokeweed-stimulated bovine peripheral blood mononuclear cells (P < 0.05). This chimeric protein may be a potent mucosal immunogen.
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PMID:A chimeric protein comprised of bovine herpesvirus type 1 glycoprotein D and bovine interleukin-6 is secreted by yeast and possesses biological activities of both molecules. 998 63

Eleven children with acute encephalopathy associated with an influenza virus infection were treated during the 1997-1998 influenza season. Reverse transcription-polymerase chain reaction (RT-PCR) assay was used to detect the viral genome in peripheral blood and cerebrospinal fluid (CSF) samples. The results were compared with those of control influenza patients without neurological complications. Viral RNA was detected only in the peripheral blood mononuclear cells of one patient with influenza-virus-associated encephalopathy (1 of 9; 11%) and in the CSF of another patient (1 of 11;9%). RT-PCR was negative in the blood of all the controls, but the percentage of RT-PCR-positive samples in the two groups was not significantly different. Cytokines and soluble cytokine receptors in plasma and CSF were then quantified using an enzyme-linked immunosorbent assay. The CSF concentrations of soluble tumor necrosis factor receptor-1 were elevated in two patients and interleukin-6 (IL-6) was elevated in one patient with influenza-virus-associated encephalopathy. On the other hand, the plasma concentrations of IL-6 were elevated in four of nine patients. The number of encephalopathy patients who had elevated plasma concentrations of IL-6 100 pg/ml was significantly higher than that of controls (P= .01). In conclusion, the infrequent detection of the viral genome in the CSF and blood showed that direct invasion of the virus into the central nervous system was an uncommon event. Proinflammatory cytokines and soluble cytokine receptors may mediate the disease. The high plasma concentration of IL-6 could be an indicator of the progression to encephalopathy.
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PMID:Detection of influenza virus RNA by reverse transcription-PCR and proinflammatory cytokines in influenza-virus-associated encephalopathy. 1042 11

Influenza infection or administration of bacterial endotoxin (lipopolysaccharide, LPS) results in diminished feeding and loss of body weight. It has been suggested that these effects may be mediated by cytokines, such as interleukin-1 (IL-1), interleukin-6 (IL-6), and/or tumor necrosis factor-alpha (TNFalpha). To assess the potential role of these cytokines, we tested the ability of the naturally occurring IL-1-receptor antagonist (IL-1ra), a monoclonal antibody to mouse IL-6 (IL-6mAb), and a TNF binding protein fragment (TNFbp) to antagonize hypophagia induced by intraperitoneally (ip) injected mouse IL-1beta or LPS or by inoculation with influenza virus. Feeding was assessed by measuring the daily intake of food pellets and sweetened milk in a 30-min period. The hypophagia induced by mIL-1beta or LPS was not affected by pretreatment with IL-6mAb. The effects of IL-1beta were blocked by IL-1ra but unaffected by TNFbp. TNFbp and IL-1ra given separately both exhibited a tendency to attenuate LPS-induced hypophagia. The effectiveness of TNFbp plus IL-1ra treatment was similar to that of the individual antagonists. However, combined treatment with TNFbp, IL-1ra, and IL-6mAb almost completely prevented the depressing effect of LPS on milk intake. The antagonists were also tested in influenza virus-inoculated mice. IL-1ra was delivered chronically by osmotic minipumps and was supplemented by treatment with TNFbp and IL-6mAb. The treatments slightly attenuated the effects of the virus on milk intake 48 h after the inoculation and delayed the decrease in body weight. However, over the entire course of the experiment, the treatment produced very small, statistically nonsignificant, attenuations of the depressions in milk and food pellet intake. Similar results were obtained with TNFbp alone or the combination of IL-6mAb and TNFbp. The results suggest that IL-1beta, TNFalpha, and IL-6 contribute to the hypophagia induced by LPS. However, antagonism of all three cytokines was not sufficient to prevent the decreases in feeding and loss of body weight induced by influenza virus infection.
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PMID:The roles of IL-1, IL-6, and TNFalpha in the feeding responses to endotoxin and influenza virus infection in mice. 1046 26

The modified vaccinia virus Ankara (MVA) strain is a candidate vector for vaccination against pathogens and tumors, due to safety concerns and the proven ability of recombinants based on this vector to trigger protection against pathogens in animals. In this study we addressed the fate of the MVA vector in BALB/c mice after intraperitoneal inoculation in comparison with that of the replication-competent Western Reserve (WR) strain by measuring levels of expression of the reporter luciferase gene, the capability to infect target tissues from the site of inoculation, and the length of time of virus persistence. We evaluated the extent of humoral and cellular immune responses induced against the virus antigens and a recombinant product (beta-galactosidase). We found that MVA infects the same target tissues as the WR strain; surprisingly, within 6 h postinoculation the levels of expression of antigens were higher in tissues from MVA-infected mice than in tissues from mice infected with wild-type virus but at later times postinoculation were 2 to 4 log units higher in tissues from WR-infected mice. In spite of this, antibodies and cellular immune responses to viral vector antigens were considerably lower in MVA-inoculated mice than in WR virus-inoculated mice. In contrast, the cellular immune response to a foreign antigen expressed from MVA was similar to and even higher than that triggered by the recombinant WR virus. MVA elicited a Th1 type of immune response, and the main proinflammatory cytokines induced were interleukin-6 and tumor necrosis factor alpha. Our findings have defined the biological characteristics of MVA infection in tissues and the immune parameters activated in the course of virus infection. These results are of significance with respect to optimal use of MVA as a vaccine.
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PMID:Biology of attenuated modified vaccinia virus Ankara recombinant vector in mice: virus fate and activation of B- and T-cell immune responses in comparison with the Western Reserve strain and advantages as a vaccine. 1062 55

Double stranded RNA (dsRNA), an intermediate that is common during viral infection, directly induces much higher levels of expression of interleukin-6 (IL-6) mRNA than does the cytokine IL-1beta. Interferon alpha (IFNalpha) by itself does not induce expression of IL-6; nonetheless, IFNalpha pretreatment dramatically enhances IL-6 induction by dsRNA but not by IL-1beta. Mutation of either the activating transcription factor/cyclic AMP response element binding protein (ATF/CREB) or the NF-IL-6 binding element within the IL-6 promoter eliminates most responsiveness of CAT reporter constructs to either dsRNA or to IL-1beta. IFNalpha pretreatment partially restores responsiveness to dsRNA but not to IL-1beta when either the ATF/CREB site or the NF-IL-6 site is mutated, but at least one of these sites must be intact for responsiveness to be restored. Mutation of the kappaB binding site in the IL-6 promoter eliminates responsiveness to either IL-1beta or to dsRNA, and pretreatment with IFNalpha does not restore any responsiveness. Incubation with dsRNA leads to a decrease in protein translation, especially in cells that have been pretreated with IFNalpha. Nonetheless, IFNalpha pretreatment followed by dsRNA leads to very high IL-6 protein levels. These studies demonstrate that major differences exist in the induction of IL-6 at both the mRNA and protein levels by dsRNA compared to cytokines and that IFNalpha pretreatment selectively enhances IL-6 induction by dsRNA but not by IL-1beta. The high levels of IL-6 expression that result when cells encounter class I IFN prior to dsRNA suggest a mechanism for a heightened host response to viral infection with heightened production of this pleotropic cytokine.
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PMID:Interferon-alpha synergistically enhances induction of interleukin-6 by double stranded RNA in HeLa cells. 1078

The influenza virus vaccines that are commercially-available for humans, horses and pigs in the United States are inactivated, whole-virus or subunit vaccines. While these vaccines may decrease the incidence and severity of clinical disease, they do not consistently provide complete protection from virus infection. DNA vaccines are a novel alternative to conventional vaccination strategies, and offer many of the potential benefits of live virus vaccines without their risks. In particular, because immunogens are synthesized de novo within DNA transfected cells, antigen can be presented by MHC class I and II molecules, resulting in stimulation of both humoral and cellular immune responses. Influenza virus has been used extensively as a model pathogen in DNA vaccine studies in mice, chickens, ferrets, pigs, horses and non-human primates, and clinical trials of DNA-based influenza virus vaccines are underway in humans. Our studies have focused on gene gun delivery of DNA vaccines against equine and swine influenza viruses in mice, ponies and pigs, including studies employing co-administration of interleukin-6 DNA as an approach for modulating and adjuvanting influenza virus hemagglutinin-specific immune responses. The results indicate that gene gun administration of plasmids encoding hemagglutinin genes from influenza viruses is an effective method for priming and/or inducing virus-specific immune responses, and for providing partial to complete protection from challenge infection in mice, horses and pigs. In addition, studies of interleukin-6 DNA co-administration in mice clearly demonstrate the potential for this approach to enhance vaccine efficacy and protection.
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PMID:DNA vaccination against influenza viruses: a review with emphasis on equine and swine influenza. 1079 87

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