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)

Exacerbations of chronic obstructive pulmonary disease (COPD) are a major cause of morbidity and mortality and hospital admission. Respiratory viral infections, especially rhinoviruses, are a major cause of COPD exacerbations, with upper respiratory tract infections being associated with over 50% of COPD exacerbations. The presence of an upper respiratory tract infection leads to a more severe exacerbation and a longer symptom recovery time at exacerbation. Respiratory viral infections occurring during COPD exacerbations are more likely to lead to hospitalization. Sputum inflammatory markers were found to be higher in those patients with symptoms of a common cold or where rhinovirus was detected at exacerbation, thus suggesting that viral infections lead to greater airway inflammation and thus more severe exacerbations. COPD exacerbations are associated also with systemic inflammatory effects with increases in markers such as plasma fibrinogen and interleukin-6. Respiratory viruses have also been detected when the patients are stable, and this suggests that chronic viral infection may occur. Strategies to prevent viral infection will have a significant effect on the morbidity of COPD and will improve quality of life.
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PMID:Role of viruses in exacerbations of chronic obstructive pulmonary disease. 1611 23

Rhinoviruses (RV) are the major cause of the common cold and acute exacerbations of asthma and chronic obstructive pulmonary disease. Toll-like receptors (TLRs) are a conserved family of receptors that recognize and respond to a variety of pathogen-associated molecular patterns. TLR3 recognizes double-stranded RNA, an important intermediate of many viral life cycles (including RV). The importance of TLR3 in host responses to virus infection is not known. Using BEAS-2B (a human bronchial epithelial cell-line), we demonstrated that RV replication increased the expression of TLR3 mRNA and TLR3 protein on the cell surface. We observed that blocking TLR3 led to a decrease in interleukin-6, CXCL8, and CCL5 in response to poly(IC) but an increase following RV infection. Finally, we demonstrated that TLR3 mediated the antiviral response. This study demonstrates an important functional requirement for TLR3 in the host response against live virus infection and indicates that poly(IC) is not always a good model for studying the biology of live virus infection.
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PMID:Toll-like receptor 3 is induced by and mediates antiviral activity against rhinovirus infection of human bronchial epithelial cells. 1616 Jan 53

This is the case study of concurrent cytomegalovirus and respiratory syncytial virus infection in an infant who showed thrombocytosis, liver dysfunction and bronchiolitis. The combination of thrombocytosis with this co-infection is causally related to elevated levels of thrombopoietin and interleukin-6. This study represents the first such case ever recorded.
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PMID:An unusual case of thrombocytosis associated with concurrent cytomegalovirus and respiratory syncytial virus infection in an immunocompetent infant: possible roles of thrombopoietin and interleukin-6. 1623 Feb 13

Most Epstein-Barr virus (EBV)-positive tumor cells contain one of the latent forms of viral infection. The role of lytic viral gene expression in EBV-associated malignancies is unknown. Here we show that EBV mutants that cannot undergo lytic viral replication are defective in promoting EBV-mediated lymphoproliferative disease (LPD). Early-passage lymphoblastoid cell lines (LCLs) derived from EBV mutants with a deletion of either viral immediate-early gene grew similarly to wild-type (WT) virus LCLs in vitro but were deficient in producing LPD when inoculated into SCID mice. Restoration of lytic EBV gene expression enhanced growth in SCID mice. Acyclovir, which prevents lytic viral replication but not expression of early lytic viral genes, did not inhibit the growth of WT LCLs in SCID mice. Early-passage LCLs derived from the lytic-defective viruses had substantially decreased expression of the cytokine interleukin-6 (IL-6), and restoration of lytic gene expression reversed this defect. Expression of cellular IL-10 and viral IL-10 was also diminished in lytic-defective LCLs. These results suggest that lytic EBV gene expression contributes to EBV-associated lymphoproliferative disease, potentially through induction of paracrine B-cell growth factors.
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PMID:Epstein-Barr virus lytic infection contributes to lymphoproliferative disease in a SCID mouse model. 1625 35

Dengue virus infection can cause mild dengue fever (DF) or severe dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Cytokines are believed to be involved in the pathogenesis of dengue infection. However, the role of the pro-inflammatory cytokine macrophage migration inhibitory factor (MIF) in dengue infection is unclear. In this study, serum levels of MIF in adult dengue patients with different disease severity and clinical outcome were determined and compared with the levels of other cytokines, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), IL-10, and interferon gamma (IFN-gamma), in the same patients. Serum levels of MIF, IL-6, and IL-10, but not IFN-gamma or TNF-alpha, were higher in all DHF patients who died than in DHF survivors and DF patients. We conclude that in addition to IL-6 and IL-10, elevated levels of serum MIF are a potential predictor of disease severity and clinical outcome in dengue patients.
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PMID:Correlation of serum levels of macrophage migration inhibitory factor with disease severity and clinical outcome in dengue patients. 1640 59

Inflammation plays a key role in atherogenesis, perhaps promoted by bacterial and viral products present within the artery wall. Vascular smooth muscle cells (VSMC) can express certain bacterially responsive Toll-like receptors (TLR), which promote a proinflammatory and proliferative VSMC phenotype when activated, but it is unknown whether virally activated TLR can regulate VSMC phenotype. Here we tested the role in VSMC of TLR3, which is activated by double-stranded (dsRNA), a molecular signature of viruses. VSMC from multiple vessel types, including human coronary artery (HCoASMC) and mouse aorta (MAoSMC), expressed TLR3 constitutively, and HCoASMC were exquisitely sensitive to dsRNA-stimulated release of monocyte chemoattractant protein-1 (MCP-1) and interleukin-6. dsRNA-induced MCP-1 release was abolished by small interfering RNA-mediated TLR3 knockdown in HCoASMC and was absent in TLR3-/- MAoSMC but was unimpaired in TLR2-/- and in TLR4 signaling-deficient MAoSMC. Exposure to dsRNA also activated ERK1/2 and NF-kappaB in both human and murine SMC, but these effects were absent in SMC from TLR3-deficient mice, demonstrating a crucial role of TLR3 signaling. dsRNA also stimulated proliferation of HCoASMC, indicated by increased DNA synthesis, and induced persistent elevations in the intracellular levels of growth-promoting mediators, including interleukin-1alpha and phospho-ERK1/2. We conclude that exposure of HCoASMC to dsRNA elicits dramatic TLR3-mediated proinflammatory and proproliferative phenotypic changes, responses that could potentially be triggered by viral infection of cells within the arterial wall.
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PMID:Toll-like receptor 3 signaling evokes a proinflammatory and proliferative phenotype in human vascular smooth muscle cells. 1678 47

Influenza virus infection during pregnancy has been implicated as one of cause of premature delivery, abortion and stillbirth. We have reported that cultured human fetal membrane chorion cells undergoing apoptosis by influenza virus infection secrete unidentified heat-stable monocyte differentiation-inducing (MDI) factors. In this study, cellular, biological and immunochemical characteristics of MDI factors were investigated using human monocytic leukemia THP-1 cells by nitroblue tetrazolium reduction and cell adhesion assays. The treatment of THP-1 cells with culture supernatants from the influenza virus-infected chorion cells induced the nitroblue tetrazolium reduction ability, which was inhibited by the addition of superoxide dismutase and diphenyleneiodonium chloride, an inhibitor for reduced nicotinamide adenine dinucleotide phosphate oxidase. The phenomenon was also observed in human peripheral blood monocytes and histiocytic leukemia U937 cells, but not in promyelocytic leukemia HL-60 cells. The induction of nitroblue tetrazolium reduction and adhesion abilities in THP-1 cells was closely correlated with the concentrations of interleukin-6 protein in the culture supernatants. These abilities were inhibited to approximately 60% by the addition of antibodies against interleukin-6, or alpha-chain (gp80) or beta-chain (gp130) of IL-6 receptor. The induction of nitroblue tetrazolium reduction was increased by the addition of supernatants from amniochorion tissue cultures after influenza virus infection. These results indicate that chorion cell-derived interleukin-6 is partly responsible for monocyte differentiation to macrophages capable of generating superoxide anion. It is possible that these pathways represent part of the mechanism for birth complications associated with intrauterine influenza infection in pregnancy.
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PMID:Characterization of monocyte differentiation-inducing (MDI) factors derived from human fetal membrane chorion cells undergoing apoptosis after influenza virus infection. 1682 80

Viral infection and type I interferon have been implicated in the pathogenesis of biliary atresia (BA), but the expression of toll-like receptors (TLRs) that recognize viruses, as well as of type 1 interferon specific signaling molecules are still unknown in BA. Fresh liver tissues were obtained from patients in early and late stage of BA and from patients with choledochal cyst (CC), as well as from normal controls receiving liver resection for benign lesion other than cholestasis or fibrosis. Archived liver tissues from patients with neonatal hepatitis (NH) were obtained for immunohistochemical studies. TLR2, 3, 4, 7 and 9 that recognized Gram-positive bacteria, double-stranded RNA virus, lipopolysaccharide, single-stranded RNA virus and DNA virus, respectively, were studied. Real-time quantitative reverse transcription polymerase chain reaction (QRT-PCR) was used to quantitate TLR, type I interferon specific molecule MxA, interleukin-6 (IL-6) and IL-8 mRNA expression and immunohistochemistry for TLR 7 and MxA protein staining. These results show that there were significantly higher TLR7 and lower TLR3 and TLR9 mRNA expression in early stage of BA than in CC. MxA mRNA expression was also significantly higher in early stage of BA and in CC than in late stage of BA. Immunoreactive TLR7 and MxA staining was higher in early stage of BA than in late stage of BA, NH and CC, which was associated with significantly higher IL-8 mRNA expression in BA than in CC. The results implicate involvement of TLRs, particularly TLR7, and type 1 specific interferon signaling in the pathogenesis of BA, especially in early stage, which is associated with upregulation of inflammatory cytokines IL-8.
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PMID:Expression of toll-like receptors and type 1 interferon specific protein MxA in biliary atresia. 1707 76

Both innate and adaptative immune responses contribute to the control of infectious diseases, including by limiting the spreading of zoonotic diseases from animal reservoirs to humans. Pigs represent an important animal reservoir for influenza virus infection of human populations and are also naturally infected by coronaviruses, an important group of viruses, which includes the recently emerged severe acute respiratory syndrome (SARS) virus. Studies on both innate and adaptative immune responses of pigs to influenza virus and coronaviruses contribute, therefore, to a better control of these infections in their natural hosts and will be briefly reviewed in this article. Pro-inflammatory cytokines, including type I interferon (IFN), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6), were found in lung secretions of influenza virus infected pigs, and correlated with the intensity of clinical signs, whereas prior vaccination against influenza strongly reduced the production of infectious virus and cytokines in the lungs upon challenge, which was associated with clinical protection. An early type I IFN production was also found in coronavirus infected pigs, including at mucosal sites. IFN induction by coronavirus is shown to involve interaction between a viral glycoprotein and a leukocyte subset, likely equivalent to plasmacytoid dendritic cells, present in the mucosae and associated lymphoid tissues. Given the IFN mediated antiviral and immunomodulatory effects, the use of IFN or IFN inducers may prove an efficient strategy for a better control of influenza virus and coronavirus infections in pigs. Because influenza and coronaviruses target mucosal surfaces, adaptative immune responses have to be characterized at mucosal sites. Thus, nasal and pulmonary antibody responses were analyzed in influenza virus infected or vaccinated pigs showing short-lived, but potentially protective local IgA and IgG antibody (Ab) responses. Interestingly, primary influenza virus infection induced long-lived increase of lung CD8(+) T cells and local lymphoproliferative responses. Pigs infected by a respiratory coronavirus (PRCV) showed virus-specific IgG Ab-secreting cells in the bronchial lymph nodes, whereas the transmissible gastroenteritis coronavirus (TGEV) induced more IgA Ab-secreting cells in gut tissues, which illustrates the importance of the route of antigen administration for inducing local immune effector mechanisms. Porcine viral infections provide, therefore, valuable models for evaluating the immune parameters that are important for controlling transmission of important viral zoonotic infections.
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PMID:Porcine innate and adaptative immune responses to influenza and coronavirus infections. 1713 2

When viral infection occurs, this information is transmitted to the brain, and symptoms such as fever and tiredness are induced. One of the causes of these symptoms is the secretion of proinflammatory cytokines in blood and the brain. In this study, the i.p. administration of polyinosinic:polycytidylic acid (poly I:C), a synthetic double-stranded RNA, to rats was used as an infection model. Poly I:C decreased spontaneous motor activity (SMA) 2 h after i.p. administration, and this decrease was maintained thereafter. The concentration of active transforming growth factor-beta (TGF-beta) in cerebrospinal fluid (CSF) increased 1 h after the administration. This increase occurred earlier than those in the concentrations of other proinflammatory cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), in serum. The intracisternal administration of an anti-TGF-beta antibody partially inhibited fever induced by poly I:C administration; however, this treatment did not affect the decrease in SMA. Furthermore, intracisternal administration of TGF-beta raised the body temperature. These results indicate that TGF-beta in the brain, which was increased by poly I:C administration, is associated with fever but not with a decrease in SMA.
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PMID:Increase in transforming growth factor-beta in the brain during infection is related to fever, not depression of spontaneous motor activity. 1715 28


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