Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P10145 (IL-8)
 23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Even though ferrets are one of the principal animal models for influenza pathogenesis, the lack of suitable immunological reagents has so far limited their use in host response studies. Using recently established real-time PCR assays for a panel of ferret cytokines, we analyzed the local ferret immune response to human influenza isolates of the H1N1 and H3N2 subtypes that varied in their virulence. We observed that the severity of clinical signs correlated with gross- and histopathological changes in the lungs and was subtype-independent. Strains causing a mild disease were associated with a strong and rapid innate response and upregulation of IL-8, while severe infections were characterized by a lesser induction of type I and II interferons and strong IL-6 upregulation. These findings suggest that more virulent strains may interfere more efficiently with the host response at early disease stages.
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PMID:Severe seasonal influenza in ferrets correlates with reduced interferon and increased IL-6 induction. 1842 Feb 48

Influenza virus infection of the respiratory tract is characterized by a neutrophil infiltrate accompanied by inflammatory cytokine and chemokine production. We and others have reported that Toll-like receptor (TLR) proteins are present on human neutrophils and that granulocyte-macrophage colony-stimulating factor (GM-CSF) treatment enhances IL-8 (CXCL8) secretion in response to stimulation with TLR ligands. We demonstrate that influenza virus can induce IL-8 and other inflammatory cytokines from GM-CSF-primed human neutrophils. Using heat inactivation of influenza virus, we show that viral entry but not replication is required for cytokine induction. Furthermore, endosomal acidification and viral uncoating are necessary. Finally, using single-cell analysis of intracellular cytokine accumulation in neutrophils from knockout mice, we prove that TLR7 is essential for influenza viral recognition and inflammatory cytokine production by murine neutrophils. These studies demonstrate neutrophil activation by influenza virus and highlight the importance of TLR7 and TLR8 in that response.
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PMID:Toll-like receptor-mediated activation of neutrophils by influenza A virus. 1854 85

The most dramatic example of defining the pathogenicity of influenza virus A/H5N1 strains is the higher fatality rate of avian influenza epidemic (>50%) occured in Southeast Asia in 1997 comparing to the pandemic caused by influenza virus A/H1N1 in 1918 (5-10%) which was recorded as the most destructive pandemic in the world. When considering the fatal/total case numbers (208/340) reported by World Health Organization in respect of December 14th, 2007, the mortality rate has now reached to 61 percent. Recent studies have shown that the high fatality rate of avian influenza virus infections is a consequence of an overactive inflammatory response and the severity of infection is closely related with virus-induced cytokine dysregulation. The most important feature of A/H5N1 immunopathogenesis is the appearence of hypercytokinemia ("cytokine storm") which is characterized by the extreme (exaggerated) production and secretion of large numbers and excessive levels of pro-inflammatory cytokines. This phenomenon is blamed on the emergence of lethal clinical symptoms such as extensive pulmonary oedema, acute bronchopneumoniae, alveolar haemorrhage, reactive haemophagocytosis, and acute respiratory distress syndrome, associated with necrosis and tissue destruction. Numerous in vitro, in vivo and clinical studies have pointed out that A/H5N1 viruses are very strong inducers of various cytokines and chemokines [Tumor Necrosis Factor (TNF)-alpha, Interferon (IFN)-gamma, IFN-alpha/beta, Interleukin (IL)-6, IL-1, MIP-1 (Macrophage Inflammatory Protein), MIG (Monokine Induced by IFN-gamma), IP-10 (Interferon-gamma-Inducible Protein), MCP-1 (Monocyte Chemoattractant Protein), RANTES (Regulated on Activation Normal T-cell Expressed and Secreted), IL-8], in both humans and animals. The privileged cells of cytokine storm are macrophages and CD8+ T-lymphocytes, while the primary contributor cytokines are TNF-alpha, IL-6 and IFN-gamma. It has been detected that, mutations of some viral genes (NS1, PB2, HA and NA) are responsible for the cytokine storm, by increasing the viral replication rate, expending the tissue tropism, facilitating the systemic invasion and emerging of resistance against the host antiviral response. It has been shown that Glu92 and Ala149 mutations, and carboxyl-terminal ESEV/EPEV motif of NS1 protein have been implicated as determinants of virulence for A/H5N1 strains. In addition, Lys627 mutation in PB2 protein, polybasic aminoacid mutations in the cleavage region of hemagglutinin (HA) polyprotein, and glycosylation and sialylation mutations in HA and neuraminidase (NA) proteins were found to enhance the immune-mediated patology of highly virulent A/H5N1 strains. In this review article, the immunopathogenesis of influenza infection and the mechanisms of cytokine storm caused by influenza A/H5N1 viruses have been discussed under the light of recent literature.
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PMID:[Cytokine storm in avian influenza]. 1869 37

Serum concentrations of cytokines (IFN-gamma, TNF-alpha, IL-2, IL-4, IL-6, IL-8) and antibody levels to influenza virus antigens were studied in adults vaccinated with split-vaccine against influenza. Analysis of antibody titers 21 days after vaccination compared with baseline levels revealed high immunogenicity of vaccine in terms of mean geometric titers increase as well as sufficient levels of seroprotection and seroconversion. Study of cytokine profile showed absence of significant changes of IFN-gamma, TNF-alpha, IL-2, IL-4 levels and considerable variability of IL-6 and IL-8 baseline levels as well as their dynamics after vaccination. Direct correlation between IL-6 and IL-8 levels was observed during whole period post-immunization. Inverse correlation between IFN-gamma and fold increase of antibody level was established which can be used as prognostic criterion of influenza prevention effectiveness.
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PMID:[Cytokine profile and level of antibodies after administration of split-vaccine against influenza to adults]. 1900 32

Intranasal corticosteroids (CS) are potentially useful interventions for children with obstructive sleep apnoea (OSA), and may reduce lymphadenoid tissue size in the upper airway. The present authors hypothesised that CS would reduce cellular proliferation and the production of pro-inflammatory cytokines in a tonsil/adenoid mixed-cell culture system. Dissociated tonsils or adenoids harvested intra-operatively from children with polysomnographically diagnosed OSA were cultured in control medium (CO) or after stimulation with lipopolysaccharide and concanavalin A (STIM), and incubated with dexamethasone (DEX; 10(-5)-10(-7) M), fluticasone (FLU; 10(-5)-10(-14) M) and budesonide (BUD; 10(-4)-10(-14) M). Proliferation and apoptosis were assessed, and supernatants were assayed for the cytokines tumour necrosis factor (TNF)-alpha, interleukin (IL)-6 and IL-8. STIM increased tonsillar and adenoidal proliferation compared with CO (1,976+/-133 versus 404+/-69 counts min(-1); n = 54). DEX, FLU and BUD reduced cellular proliferation rates, and exhibited dose-dependent effects, with the potency being FLU>BUD>DEX (n = 25 per group). Conversely, CS increased cellular apoptosis (n = 20 per group). Furthermore, TNF-alpha, IL-8 and IL-6 concentrations in the supernatant were increased by STIM, and markedly reduced by all CS (n = 48 per group). Whole tissue cell cultures of adenoids and tonsils provide a useful approach for in vitro assessment of therapeutic efficacy of corticosteroids in the management of lymphadenoid hypertrophy that underlies obstructive sleep apnoea in children.
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PMID:Corticosteroids suppress in vitro tonsillar proliferation in children with obstructive sleep apnoea. 1904 10

Numerous Echinacea preparations are available on the market for the prevention and treatment of cold and 'flu symptoms and inflammatory conditions associated with infections. Most of these preparations are consumed orally in the form of aqueous or ethanol extracts and tinctures. Since the recommended consumption normally involves a brief local exposure to the diluted preparation at an unspecified time in relation to the actual infection, then it is important that experimental models for the evaluation of Echinacea reflect these limitations. A line of human bronchial epithelial cells, in which rhinoviruses stimulate the production of pro-inflammatory cytokines, was used to evaluate several relevant parameters. The chemically characterized Echinacea preparation (Echinaforce) was capable of inhibiting completely the rhinovirus induced secretion of IL-6 (interleukin-6) and IL-8 (chemokine CXCL-8) in these cells, regardless of whether the Echinacea was added before or after virus infection, and in response to a range of virus doses. This inhibitory effect was also manifest under conditions resembling normal consumption with respect to the duration of exposure to Echinacea and the Echinacea dilution. It is concluded that under real life conditions of Echinacea consumption, the virus-induced stimulation of pro-inflammatory cytokines can be effectively reversed or alleviated.
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PMID:Echinacea as an antiinflammatory agent: the influence of physiologically relevant parameters. 1910 35

Alveolar type II epithelial cells (ATIIs) are one of the primary targets for influenza A pneumonia. The lack of a culture system for maintaining differentiated ATIIs hinders our understanding of pulmonary innate immunity during viral infection. We studied influenza A virus (IAV)-induced innate immune responses in differentiated primary human ATIIs and alveolar macrophages (AMs). Our results indicate that ATIIs, but not AMs, support productive IAV infection. Viral infection elicited strong inflammatory chemokine and cytokine responses in ATIIs, including secretion of IL-8, IL-6, MCP-1, RANTES, and MIP-1beta, but not TNF-alpha, whereas AMs secreted TNF-alpha as well as other cytokines in response to infection. Wild-type virus A/PR/8/34 induced a greater cytokine response than reassortant PR/8 virus, A/Phil/82, despite similar levels of replication. IAV infection increased mRNA expression of IFN genes IFN-beta, IL-29 (IFN-lambda1), and IL-28A (IFN-lambda2). The major IFN protein secreted by type II cells was IL-29 and ATIIs appear to be a major resource for production of IL-29. Administration of IL-29 and IFN-beta before infection significantly reduced the release of infectious viral particles and CXC and CC chemokines. IL-29 treatment of type II cells induced mRNA expression of antiviral genes MX1, OAS, and ISG56 but not IFN-beta. IL-29 induced a dose-dependent decrease of viral nucleoprotein and an increase of antiviral genes but not IFN-beta. These results suggest that IL-29 exerts IFN-beta-independent protection in type II cells through direct activation of antiviral genes during IAV infection.
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PMID:Differentiated human alveolar type II cells secrete antiviral IL-29 (IFN-lambda 1) in response to influenza A infection. 1915 75

Several viruses associated with upper respiratory diseases have been shown to stimulate the secretion of pro-inflammatory cytokines, including chemokines, sometimes in the absence of viral cytopathology. We evaluated the ability of a standardized preparation of the popular herbal medicine Echinacea (Echinaforce, an ethanol extract of herb and roots of E. purpurea, and containing known concentrations of marker compounds) to inhibit the viral induction of various cytokines in a line of human bronchial epithelial cells (BEAS-2B), and in two other human cell lines. All of the viruses tested, rhinoviruses 1A and 14, influenza virus, respiratory syncytial virus, adenovirus types 3 and 11, and herpes simplex virus type 1, induced substantial secretion of IL-6 and IL-8 (CXCL8), in addition to several other chemokines, depending on the virus, although only viable viruses were able to do this. In every case however Echinacea inhibited this induction. The Echinacea preparation also showed potent virucidal activity against viruses with membranes, indicating the multi-functional potential of the herb. These results support the concept that certain Echinacea preparations can alleviate "cold and flu" symptoms, and possibly other respiratory disorders, by inhibiting viral growth and the secretion of pro-inflammatory cytokines.
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PMID:Induction of multiple pro-inflammatory cytokines by respiratory viruses and reversal by standardized Echinacea, a potent antiviral herbal extract. 1940 31

The antioxidant N-acetyl-L-cysteine (NAC) had been shown to inhibit replication of seasonal human influenza A viruses. Here, the effects of NAC on virus replication, virus-induced pro-inflammatory responses and virus-induced apoptosis were investigated in H5N1-infected lung epithelial (A549) cells. NAC at concentrations ranging from 5 to 15 mM reduced H5N1-induced cytopathogenic effects (CPEs), virus-induced apoptosis and infectious viral yields 24 h post-infection. NAC also decreased the production of pro-inflammatory molecules (CXCL8, CXCL10, CCL5 and interleukin-6 (IL-6)) in H5N1-infected A549 cells and reduced monocyte migration towards supernatants of H5N1-infected A549 cells. The antiviral and anti-inflammatory mechanisms of NAC included inhibition of activation of oxidant sensitive pathways including transcription factor NF-kappaB and mitogen activated protein kinase p38. Pharmacological inhibitors of NF-kappaB (BAY 11-7085) or p38 (SB203580) exerted similar effects like those determined for NAC in H5N1-infected cells. The combination of BAY 11-7085 and SB203580 resulted in increased inhibitory effects on virus replication and production of pro-inflammatory molecules relative to either single treatment. NAC inhibits H5N1 replication and H5N1-induced production of pro-inflammatory molecules. Therefore, antioxidants like NAC represent a potential additional treatment option that could be considered in the case of an influenza A virus pandemic.
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PMID:N-acetyl-L-cysteine (NAC) inhibits virus replication and expression of pro-inflammatory molecules in A549 cells infected with highly pathogenic H5N1 influenza A virus. 1973 54

The mitogen-activated protein kinase (MAPK) family is responsible for important signalling pathways which regulate cell activation, differentiation, apoptosis and immune responses. Studies have shown that influenza virus infection activates MAPK family members in mammals. While the extracellular signal-regulated kinase (ERK)1/2 is important for virus replication, activation of p38 controls the expression of RANTES, interleukin (IL)-8 and tumour necrosis factor (TNF)-alpha. In this study, we report that avian influenza virus (AIV) activates ERK, p38 and Jun-N-terminal kinases in avian species. In chicken macrophages, while ERK was required for H9N2 AIV replication, ERK regulated proinflammatory cytokines IL-1beta, IL-6 and IL-8, which is distinct from what has been previously reported in mammalian cells. Moreover, ERK alone suppressed TNF-alpha and FasL and inhibited TNF-family-mediated extrinsic apoptosis in H9N2-infected chicken macrophages. Taken together, these findings suggest that ERK signalling may uniquely play important roles in avian host responses to AIV infection.
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PMID:Roles of the ERK MAPK in the regulation of proinflammatory and apoptotic responses in chicken macrophages infected with H9N2 avian influenza virus. 1986


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