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)

Following infection with influenza virus, animals display decreased locomotor activity and feeding behavior 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 tumor necrosis factor alpha (TNF-alpha), induced by the infection. To assess the potential role of IL-1, we tested the ability of a naturally occurring IL-1-receptor antagonist (IL-1ra) to antagonize the changes in feeding behavior induced by IL-1, endotoxin (lipopolysaccharide, LPS), and infection with influenza virus. Feeding behavior was assessed by measuring the daily intake of food pellets and sweetened milk in a 30-min period. Acute injection of IL-1 beta decreased milk intake, but mouse IL-6 and mouse TNF-alpha did not. However, TNF-alpha decreased food pellet intake slightly, especially when it was injected at the beginning of the dark phase. The reductions in milk intake induced by mouse IL-1 beta were largely prevented by IL-1ra pretreatment (100 micrograms/mouse i.p.). The LPS-induced reductions in milk intake were attenuated, but not blocked, by IL-1ra treatment (300 micrograms/mouse). LPS still induced significant decrements in the presence of the antagonist. In influenza virus-infected mice, IL-1ra was administered either by repeated subcutaneous (s.c.) injections, or by continuous s.c. infusion from osmotic minipumps. These IL-1ra treatments produced small, but statistically significant, attenuations of the depression in milk and food pellet intake in the virus-infected mice. In several experiments, IL-1ra treatment increased the survival of influenza virus-infected mice. Thus the attenuation of the hypophagia may have been caused by this IL-1ra-induced increase in survival. The results suggest that IL-1 contributes to sickness behavior induced by LPS and influenza virus infection, but it is not the only factor involved.
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PMID:The role of cytokines in the behavioral responses to endotoxin and influenza virus infection in mice: effects of acute and chronic administration of the interleukin-1-receptor antagonist (IL-1ra). 943

This study was conducted to investigate whether Accell gene gun coadministration of DNA encoding human interleukin-6 (IL-6) would enhance protective immune responses in mice to an equine influenza A virus hemagglutinin (HA) DNA vaccine. Mice that received HA DNA alone exhibited accelerated clearance of homologous challenge virus but were not protected from infection. In contrast, mice that received both HA and IL-6 DNA had no detectable virus in their lungs after challenge. These results strongly support the use of IL-6 as a cytokine adjuvant in DNA vaccination.
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PMID:Coadministration of DNA encoding interleukin-6 and hemagglutinin confers protection from influenza virus challenge in mice. 944 82

The present phase II study was undertaken to assess antitumoral activity, safety and tolerability of recombinant human interleukin-6 (rh IL-6) in patients with advanced renal cell cancer. Rh IL-6 was administered as a daily subcutaneous injection at a fixed dose of 150 micrograms/day for a maximum of 42 consecutive days. 12 patients with metastatic renal cell cancer without previous immunotherapy were enrolled and were evaluated for response. No objective clinical responses were observed in the trial. Toxicity was moderate and reversible and mainly comprised fever, influenza-like symptoms, fatigue and moderate hepatotoxicity. Anaemia, leucocytosis, thrombocytosis and induction of an acute phase response were observed in most patients. In conclusion, prolonged subcutaneous administration of rh IL-6 on an outpatient basis is safe and feasible. However, rh IL-6 exhibited no antitumoral activity in patients with metastastic renal cell cancer. Profound regulatory effects on haematopoiesis and inflammatory response of rh IL-6 were observed.
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PMID:Lack of efficacy of recombinant human interleukin-6 in patients with advanced renal cell cancer: results of a phase II study. 971 86

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

The serum concentrations of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma) were measured by enzyme immunoassays in 44 patients with Chlamydia (n = 13) or Mycoplasma (n = 14) pneumonia or influenza A infection (n = 17) and in 20 control subjects. The levels of IFN-gamma were raised in 29/44 patients. The concentrations of IL-6 were raised in 32/44 patients. Raised levels of TNF-alpha were seen in 26/44 but there was no significant difference between the levels of the different groups of patients. All three cytokines indicated clinical recovery when acute and convalescent samples from 10 patients with Chlamydia pneumonia were analyzed. IFN-gamma, IL6 and TNF-alpha are present in the circulation in the majority of patients with Chlamydia and Mycoplasma pneumonia and in influenza A infection. We suggest that repeated measurement of cytokines, such as IL-6, IFN-gamma and TNF-alpha, may be useful in the management of lower respiratory tract infections but further studies are needed to define the value of cytokine measurements in acute pneumonia.
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PMID:Cytokine responses in patients with pneumonia caused by Chlamydia or Mycoplasma. 973 Jul 97

Interferon (IFN)-inducible human MxA protein mediates resistance against influenza and several other RNA viruses. The MxA gene is under the control of type I IFN and, in certain cell types, is also directly activated by viruses. Here we show that in human macrophages, MxA mRNA levels are upregulated by very low doses of IFN-alpha in a dose-dependent manner. A similar, albeit much weaker, dose-dependent induction was seen with IFN-gamma. The induction was rapid and independent of protein synthesis. Interleukin-6 (IL-6) or tumor necrosis factor-alpha (TNF-alpha) did not influence MxA mRNA levels alone or in combination with IFNs, in spite of the presence of putative response elements of these cytokines in the MxA promoter. We show that the promoter of the MxA gene contains two functional IFN-stimulated response elements (ISRE) near the transcription start site and one homologous ISRE-like element, which is apparently nonfunctional, further upstream. The two proximal ISRE sites are essential for IFN-alpha-induced transcription and appear to be binding sites for IFN-stimulated gene factor 3 complex. In addition, EMSA and DNAse I footprinting analysis demonstrated that Spl binds with high affinity to a region encompassing nucleotides -25 and -50 and, thus, may provide means of interaction with the basal transcriptional machinery.
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PMID:The proximal interferon-stimulated response elements are essential for interferon responsiveness: a promoter analysis of the antiviral MxA gene. 978 17

The coadministration of cytokines can modulate immunity in DNA based viral vaccines. In order to determine the effects of various cytokines on long-term protection against the influenza virus, mice were intramuscularly coinoculated with plasmids that encoded either the granulocyte-macrophage colony-stimulating factor (GMCSF), interleukin-4 (IL-4), interleukin-12 (IL-12), or the interleukin-6 (IL-6) gene, in the presence of two plasmids that encoded the nucleoprotein (NP) and the hemagglutinin (HA) gene of the influenza A virus. The coadministration of IL-4, IL-6 and IL-12 transiently enhanced antibody responses against influenza virus in early time points (4 to 7 week post immunization) after post inoculation. The expression of GMCSF gene resulted in the sustained elevation of antibody responses for at least 20 weeks post inoculation. However, NP-specific CTL responses decreased in these animals. Mice that received either the IL-12 or the IL-6 gene had enhanced NP-specific CTL responses. Remarkably, the coadministration of the IL-6 gene completely protected mice from a lethal challenge with influenza virus. Conversely, mice that received the IL-4 gene appeared to be more susceptible to lethal challenge than mice that were inoculated with the NP and the HA genes alone. These results demonstrate that the use of cytokines as molecular adjuvants when coadministered in influenza DNA vaccination must be specific. Our data also demonstrates that the coadministration of IL-6 should be considered to enhance the efficacy of influenza DNA vaccines.
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PMID:IL-6 induces long-term protective immunity against a lethal challenge of influenza virus. 1007 28

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

Uncomplicated influenza in humans, horses or swine is characterized by massive virus replication in respiratory epithelial cells, inflammation and an abrupt onset of general and respiratory disease. There is now growing evidence that the so-called early cytokines produced at the site of infection mediate many of the clinical and pathological manifestations. Among these cytokines are interferon-alpha (IFN-alpha), tumour necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1) alpha and beta, interleukin-6 (IL-6), interleukin-8 (IL-8) and monocyte-attracting chemokines. This paper reviews: (1) in vivo examinations of the cytokine profiles during influenza in mice, humans or swine; (2) in vivo data on the probable role of these cytokines; and (3) selected in vitro data on cytokine induction by the influenza virus. Examination of respiratory secretions of experimentally infected humans or animals revealed a brisk and concurrent rise in several of the cytokines mentioned. Moreover, peak cytokine levels directly correlated with virus replication and disease. In the mouse model, specific anti-cytokine strategies have further confirmed the role of cytokines in body temperature changes, anorexia and lung inflammation. However, cytokines were clearly not the only factor contributing to disease, and they seemed to be essential for resolution of the infection. Though influenza virus was shown to induce cytokines in cell culture, in vitro experiments have also revealed conflicting data. Furthermore, the viral genes or products that are responsible for cytokine induction are unknown. Exactly this information would make important contributions to our understanding of the genetic basis of viral virulence.
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PMID:Cytokines in the pathogenesis of influenza. 1079 83


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