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)

Respiratory syncytial virus (RSV), the most common etiologic agent of epidemic pediatric respiratory disease, infects and replicates in the human airway epithelium, resulting in the induction of cellular gene products essential for immune and inflammatory responses. We describe the effect of RSV infection on nuclear factor-IL6 (NF-IL6) expression, a human basic domain-leucine zipper-containing transcription factor that alone in combination with other inducible transcription factors regulates the expression of cytokine and adhesion molecule genes. RSV-infected human type II pulmonary alveolar epithelial cells (A549) synthesize a single 45.7-kDa isoform of NF-IL6 rapidly and in a time-dependent manner. NF-IL6 is first detectable after 3 h of infection and continues to accumulate until 48 h (until the cells lose viability). NF-IL6 production could not be induced by UV-inactivated virus, demonstrating the requirement of viral replication for NF-IL6 synthesis. Immunoprecipitation after [35S]methionine metabolic labeling was done to investigate the mechanism for NF-IL6 production. There was robust NF-IL6 protein synthesis within RSV-infected (24 h) cells. Protein synthesis occurred without detectable changes in the abundance or size of the single 1.8-kb NF-IL6 mRNA. RNase protection assay of transfected chloramphenicol acetyltransferase reporter genes driven by either wild-type or mutated NF-IL6 binding sites show a virus-induced increase in NF-IL6-dependent transcription. These studies have demonstrated a novel inducible mechanism for translational control of NF-IL6 synthesis and identify this transcription factor as a potential effector of the host response to RSV infection.
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PMID:Inducible translational regulation of the NF-IL6 transcription factor by respiratory syncytial virus infection in pulmonary epithelial cells. 862 74

Chronic lung disease of prematurity (CLD) is a common respiratory disorder of preterm infants. At autopsy, fibroblast proliferation, and components of the extracellular matrix, including collagen and fibronectin, are markedly increased in the lungs of infants who die from CLD. Examination of broncho-alveolar fluid suggests that the persistence of neutrophils is associated with the development of CLD. In our studies, the pro-inflammatory cytokines, interleukin-1 beta (IL-1 beta) and interleukin-6, (IL-6) and mediators which reflect neutrophil recruitment and activation, including soluble intercellular adhesion molecule, interleukin-8 (IL-8) and neutrophil elastase, were increased in lavage fluid obtained from infants who developed CLD when compared to infants who did not. Furthermore, semiquantitative reverse transcriptase-polymerase chain reaction of mRNA extracted from lavage cells suggested that luminal cells may be the source of IL-6 detected in lavage fluid but non-luminal cells may be the sources of IL-1 beta and IL-8. Fibrosis is thought to be mediated by the pro-fibrotic cytokines including transforming growth factor-beta1 (TGF-beta 1). Both active and total TGF-beta 1 were increased in lavage fluid from infants who developed CLD. Furthermore, both type I procollagen and TGF-beta were increased qualitatively in lung tissue obtained at autopsy from infants who died from respiratory failure. The increase in inflammatory mediators was maximal at 10 days of age. By contrast, the increase in TGF-beta 1 was maximal at 4 days of age. This suggests that the interaction between inflammation and fibrosis in CLD is complex, and that prenatal factors may be important in the pathogenesis of CLD.
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PMID:Cytokines in chronic lung disease of prematurity. 883 40

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

Rhinoviruses are the major cause of the common cold and a trigger of acute asthma exacerbations. Whether these exacerbations result from direct infection of the lower airway or from indirect mechanisms consequent on infection of the upper airway alone is currently unknown. Lower respiratory infection was investigated in vitro by exposing primary human bronchial epithelial cells to rhinoviruses and in vivo after experimental upper respiratory infection of human volunteers. Bronchial infection was confirmed by both approaches. Furthermore, rhinoviruses induced production of interleukin-6, -8, and -16 and RANTES and were cytotoxic to cultured respiratory epithelium. This evidence strongly supports a direct lower respiratory epithelial reaction as the initial event in the induction of rhinovirus-mediated asthma exacerbations. The frequency of infection and the nature of the inflammatory response observed are similar to those of the upper respiratory tract, suggesting that rhinovirus infections may be one of the most important causes of lower in addition to upper respiratory disease.
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PMID:Rhinoviruses infect the lower airways. 1083 65

Periodontopathic anaerobes such as Porphyromonas gingivalis are frequently found in aspiration pneumonia and lung abscesses. However, defense mechanisms and responses to these bacterial infections in the lung in vivo remain poorly understood. The coexistence of P. gingivalis with Treponema denticola has been found at higher levels and proportions in periodontally diseased sites. We hypothesized that mixed infections with P. gingivalis and T. denticola can cause severe respiratory disease. In the present study, inflammatory responses to mono- and mixed inoculations with P. gingivalis and T. denticola in the bronchoalveolar lavage (BAL) fluid were investigated. Acute pneumonia and lung abscesses in mice with the mixed infection resulted in a 40% mortality rate within 72 h, compared with only 10% mortality for the respective monoinfections. Pulmonary clearance of P. gingivalis was delayed in the mice with mixed infections with P. gingivalis and T. denticola. Tumor necrosis factor alpha (TNFalpha) interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) levels from BAL fluid of mice with mixed infections at 24 h after inoculation were significantly higher than those after P. gingivalis monoinfection (TNFalpha: P < 0.05, Il-1beta: P < 0.001, IL-6: P < 0.05). The chemokine KC level from BAL fluid of mice at 48 h (P < 0.05) and 72 h after mixed infection was also significantly increased when compared with that after P. gingivalis monoinfection (P < 0.001). The present study demonstrates that a mixed infection of P. gingivalis with T. denticola in mouse causes a marked bronchopneumonia and lung abscess in the mouse model.
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PMID:Mixed infections with Porphyromonas gingivalis and Treponema denticola cause excessive inflammatory responses in a mouse pneumonia model compared with monoinfections. 1467 Apr 48

Respiratory syncytial virus (RSV) bronchiolitis is an important cause of severe respiratory disease in infants. This study aimed to characterise changes in pulmonary pro- and anti-inflammatory responses in infants with RSV bronchiolitis over the course of the illness. On the day of intubation (Day 1) and the day of extubation (Day X), nonbronchoscopic bronchoalveolar lavage was performed on term and preterm infants ventilated for RSV bronchiolitis and on control infants on Day 1. Tumour necrosis factor (TNF)-alpha, soluble TNF receptor (sTNFR) and interleukin (IL)-6 messenger ribonucleic acid (mRNA) and protein were measured. Twenty-four infants, born at term and 23 infants born preterm with RSV bronchiolitis and 10 controls were recruited. TNF-alpha and IL-6 mRNA and protein in infants with bronchiolitis were greater than the control group on Day 1. In preterm infants, who were ventilated for longer than term infants, TNF-alpha and IL-6 proteins decreased between Day 1 and Day X. Concentrations of sTNFRs differed between groups on Day 1, but levels did not change between Day 1 and Day X. Large amounts of tumour necrosis factor-alpha and interleukin-6 in the respiratory syncytial virus-infected lung suggest important roles for these cytokines in the pathogenesis of respiratory syncytial virus bronchiolitis. The decrease in tumour necrosis factor-alpha and interleukin-6 protein in preterm infants may reflect the prolonged clinical course seen in these infants.
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PMID:Pro- and anti-inflammatory responses in respiratory syncytial virus bronchiolitis. 1473 41

Bovine respiratory syncytial virus (BRSV) has been identified worldwide as an important pathogen associated with acute respiratory disease in calves. An infection model has been developed reflecting accurately the clinical course and the development of pathological signs during a natural BRSV-infection. In the experiments described in the present study, calves were infected at 13-21 weeks of age and reinfected 14 weeks later. Blood samples from the entire infection period were analysed for acute phase protein (haptoglobin) by ELISA and for expression (mRNA level in peripheral blood mononuclear cells) of the cytokines interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-6 (IL-6) and interferon-gamma (IFNgamma) by quantitative real-time reverse transcribed polymerase chain reaction (RT-PCR). IFNgamma, interleukin-6 and haptoglobin were markedly induced together with development of clinical signs in response to the first infection with BRSV. The IFNgamma response was biphasic, with an early peak at day 1-3 post infection (p.i.) and a later increase between day 5 and 8 p.i. Reinfection also resulted in an induction of IFNgamma, but without induction of clinical signs, IL-6 and haptoglobin. These results indicate that early mediators connected with the innate responses are induced on a first encounter with the pathogen, but not on a second encounter (reinfection) where the adaptive immune system may act as the first line defence.
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PMID:Marked induction of IL-6, haptoglobin and IFNgamma following experimental BRSV infection in young calves. 1569 May 87

Influenza A virus (IAV) is the etiological agent of a highly contagious acute respiratory disease that causes epidemics and considerable mortality annually. Recently, we demonstrated, using an in vitro approach, that the pattern recognition Toll-like receptor (TLR)3 plays a key role in the immune response of lung epithelial cells to IAV. In view of these data and the fact that the functional role of TLR3 in vivo is still debated, we designed an investigation to better understand the role of TLR3 in the mechanisms of IAV pathogenesis and host immune response using an experimental murine model. The time-course of several dynamic parameters, including animal survival, respiratory suffering, viral clearance, leukocyte recruitment into the airspaces and secretion of critical inflammatory mediators, was compared in infected wild-type and TLR3(-/-) mice. First, we found that the pulmonary expression of TLR3 is constitutive and markedly upregulated following influenza infection in control mice. Notably, when compared to wild-type mice, infected TLR3-/- animals displayed significantly reduced inflammatory mediators, including RANTES (regulated upon activation, normal T cell expressed and secreted), interleukin-6, and interleukin-12p40/p70 as well as a lower number of CD8+ T lymphocytes in the bronchoalveolar airspace. More important, despite a higher viral production in the lungs, mice deficient in TLR3 had an unexpected survival advantage. Hence, to our knowledge, our findings show for the first time that TLR3-IAV interaction critically contributes to the debilitating effects of a detrimental host inflammatory response.
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PMID:Detrimental contribution of the Toll-like receptor (TLR)3 to influenza A virus-induced acute pneumonia. 1678 35

Escherichia coli infection of the respiratory system in chickens occurs as a sequel to a variety of environmental stressors or microbial infections, culminating as chronic respiratory disease (CRD) syndrome or colibacillosis. These diseases cause significant production losses in poultry. With the growing concerns about the use of antibiotics in animal production, for diseases such as CRD, alternative natural agents, like cytokines, may be considered for enhancing health by stimulating the immune system. The current study was aimed at understanding the in vivo effects of recombinant chicken interferon-gamma (ChIFN-gamma) treatment on a variety of immunologic parameters during E. coli infection in chickens. Administration of ChIFN-gamma to chickens increased the percentage of phagocytes in lung and blood of E. coli-infected birds. At the phenotypic level, there was an increase in the percentage of cells expressing MHC II in the air sac, with a concomitant reduction in the proportion of these cells in blood. Furthermore, the blood plasma from ChIFN-gamma-treated infected birds showed an increased level of interleukin-6 (IL-6) activity. Cumulatively, these findings are indicative of in vivo enhancement of immune responses due to ChIFN-gamma. However, administration of ChIFN-gamma protein did not mitigate the development of air sac lesions following E. coli infection.
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PMID:IFN-gamma enhances immune responses to E. coli infection in the chicken. 1805 28

Although current H5N1 highly pathogenic avian influenza viruses (HPAIV) are inefficiently transmitted to humans, infected individuals can suffer from severe disease, often progressing rapidly to acute respiratory distress syndrome and multiorgan failure. This is in contrast with the situation with human influenza viruses, which in immunocompetent individuals usually cause only a respiratory disease which is less aggressive than that observed with avian H5N1 viruses. While the biological basis of inefficient transmission is well documented, the mechanisms by which the H5N1 viruses cause fatal disease remain unclear. In the present study, we demonstrate that human pulmonary microvascular endothelial cells (hPMEC) had a clearly higher susceptibility to infection by H5N1 HPAIV than to infection by human influenza viruses. This was measurable by de novo intracellular nucleoprotein production and virus replication. It was also related to a relatively higher binding capacity to cellular receptors. After infection of hPMEC, cell activation markers E-selectin and P-selectin were upregulated, and the proinflammatory cytokines interleukin-6 and beta interferon were secreted. H5N1 virus infection was also associated with an elevated rate of cell death. Reverse genetics analyses demonstrated a major role for the viral hemagglutinin in this cell tropism. Overall, avian H5N1 viruses have a particular receptor specificity targeting endothelial cells that is different from human influenza viruses, and this H5N1 receptor specificity could contribute to disease pathogenesis.
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PMID:Hemagglutinin-dependent tropism of H5N1 avian influenza virus for human endothelial cells. 1981 46


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