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

In pneumonia local phagocyte activation is crucial for clearing of pathogenic microorganisms. In this context alveolar macrophage interleukin-8 secretion, phagocyte oxidative response and concentrations of lavage proteins were quantified, including interleukin-8, in 31 patients with pneumonia, 13 age matched patients with peripheral lung consolidation and six healthy volunteers; these findings were related to the impairment of gas exchange and the bacterial load in the alveolar space. Increased interleukin-8 levels were found in bronchoalveolar lavage fluid (BALF) and in alveolar macrophage supernatants from patients with pneumonia (214 ng/10(5) AM +/- 121 vs 71 ng/10(5) AM +/- 35 and 66 ng/10(5) AM +/- 30, p < 0.05). Interleukin-8 release from alveolar macrophages correlated with the upregulated spontaneous luminol enhanced oxidative response of pulmonary phagocytes but not with the neutrophil count in BALF. In pneumonia patients a significant difference was found between patients with 10(4) or more colony forming units (CFU)/ml BALF of one pathogen and patients with less CFU or nonspecific microbiological results (261 ng/10(5) AM +/- 89 vs 179 ng/10(5) AM +/- 81 and 7.5 ng/ml BALF +/- 17 vs 0.44 ng/ml BALF +/- 1, p < 0.05). Further, a negative correlation between interleukin-8 release of alveolar macrophages and the arterial pO2 at the time of BALF could be demonstrated (r = -0.47, p < 0.05). The results demonstrate local cellular activation in community-acquired pneumonia, which is related to the bacterial load in the alveolar space and to impairment of gas exchange. This is consistent with the hypothesis that pulmonary phagocytes play a central role in the pathogenesis of bacterial pneumonia, contributing not only to bacterial clearing but also to local tissue damage.
Infection
PMID:Role of interleukin-8 in community-acquired pneumonia: relation to microbial load and pulmonary function. 910 84

The protozoan parasite Entamoeba histolytica causes amebic dysentery and amebic liver abscess, diseases associated with significant morbidity and mortality worldwide. E. histolytica infection appears to involve the initial attachment of amebic trophozoites to intestinal epithelial cells, followed by lysis of these cells and subsequent invasion into the submucosa. A recent in vitro study (L. Eckmann, S. L. Reed, J. R. Smith, and M. F. Kagnoff, J. Clin. Invest. 96:1269-1279, 1995) demonstrated that incubation of E. histolytica trophozoites with epithelial cell lines results in epithelial cell production of inflammatory cytokines, including interleukin-1 (IL-1) and IL-8, suggesting that intestinal epithelial cell production of cytokines might play a role in the inflammatory response and tissue damage seen in intestinal amebiasis. To determine whether intestinal epithelial cell production of IL-1 and IL-8 occurs in response to E. histolytica infection in vivo and as an approach to studying the specific interactions between amebic trophozoites and human intestine, we used a SCID mouse-human intestinal xenograft (SCID-HU-INT) model of disease, where human intestinal xenografts were infected with virulent E. histolytica trophozoites. Infection of xenografts with E. histolytica trophozoites resulted in extensive tissue damage, which was associated with the development of an early inflammatory response composed primarily of neutrophils. Using oligonucleotide primers that specifically amplify human IL-1beta and IL-8, we could demonstrate by reverse transcription PCR that mRNA for both IL-1beta and IL-8 is produced by human intestinal xenografts in response to amebic infection. The increase in human intestinal IL-1beta and IL-8 in response to invasive amebiasis was confirmed by enzyme-linked immunosorbent assays specific for human IL-1beta and IL-8. Using immunohistochemistry, we confirmed that human intestinal epithelial cells were the source of IL-8 in infected xenografts and established that IL-8 production can occur at sites distal to areas of intestinal mucosal damage. These results demonstrate that human intestinal epithelial cells can produce inflammatory cytokines in response to infection in vivo and establish the SCID-HU-INT model as a system for studying the interactions between E. histolytica and human intestine.
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PMID:Human intestinal epithelial cells produce proinflammatory cytokines in response to infection in a SCID mouse-human intestinal xenograft model of amebiasis. 912 40

Infection of the lung epithelial cell line A549 by respiratory syncytial virus (RSV) resulted in the elevated synthesis of multiple cellular cytokines, including a number of interleukins (ILs). Detailed studies of IL-11 induction revealed that it required infection by viable virus and involved a net increase in the steady state level of IL-11 mRNA. Nuclear run-on assays showed a direct effect of RSV on IL-11 gene transcription. Mutational analysis of the IL-11 promoter fused to a reporter luciferase gene demonstrated the requirement of a region 720 nucleotides upstream of the mRNA start site in the transcriptional induction of IL-11 by RSV. Two nearly identical 10-nucleotide-long sequences GGGGTCTCCC and GGGTCTCCCC in this region resembled the NF-kappa B consensus motif. Mutation of either sequence greatly reduced RSV-mediated induction of IL-11 promoter activity. NF-kappa B sites in IL-1 alpha, IL-6, and IL-8 promoters were also required for RSV-mediated induction of transcription of these promoters. Immunological studies and use of reporter gene constructs provided direct evidence for the activation and nuclear translocation of NF-kappa B by RSV. Sodium salicylate and aspirin, inhibitors of NF-kappa B activation, abolished transcriptional induction of all these cytokines by RSV. Together, these studies demonstrated an essential role of NF-kappa B in RSV-mediated transcription of multiple cytokines genes and suggested a possible use of salicylates in managing airway inflammation and viral pathogenesis during RSV infection.
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PMID:Transcriptional induction of multiple cytokines by human respiratory syncytial virus requires activation of NF-kappa B and is inhibited by sodium salicylate and aspirin. 919 51

Chemokines are a family of low-molecular-weight proinflammatory cytokines that have leukocyte chemotactic and activating properties. Chemokine protein and mRNA are increased in the gastric mucosa of Helicobacter pylori infection and they are considered to regulate migration of leukocyte populations. The increase of C-X-C chemokines (e.g. IL-8, GRO-alpha) which effect primarily neutrophils is significantly associated with gastric polymorphonuclear cell activity suggesting that these chemokines play a primary role in active gastritis induced by H. pylori infection. In vitro enhanced epithelial chemokine responses are induced by cagA positive strains which have been clinically associated with more severe clinical outcome. Infection with cagA-positive H. pylori strains associates in vivo specifically with a C-X-C profile and enhanced polymorphonuclear infiltration in the gastric mucosa. Whilst infection with H. pylori, especially cag positive strains, is associated with more severe disease, genetic variability in host chemokine responses may also contribute to disease outcome.
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PMID:Mucosal chemokines in Helicobacter pylori infection. 937 14

The alpha-chemokine receptor CXCR4 has recently been shown to support syncytium formation mediated by strains of feline immunodeficiency virus (FIV) that have been selected for growth in the Crandell feline kidney cell line (CrFK-tropic virus). Given that both human and feline CXCR4 support syncytium formation mediated by FIV, we investigated whether human stromal cell-derived factor (SDF-1) would inhibit infection with FIV. Human SDF-1alpha and SDF-1beta bound with a high affinity (K(D)s of 12.0 and 10.4 nM, respectively) to human cells stably expressing feline CXCR4, and treatment of CrFK cells with human SDF-1alpha resulted in a dose-dependent inhibition of infection by FIV(PET). No inhibitory activity was detected when the interleukin-2 (IL-2)-dependent feline T-cell line Mya-1 was used in place of CrFK cells, suggesting the existence of a CXCR4-independent mechanism of infection. Furthermore, neither the human beta-chemokines RANTES, MIP-1alpha, MIP-1beta, and MCP-1 nor the alpha-chemokine IL-8 had an effect on infection of either CrFK or Mya-1 cells with CrFK-tropic virus. Envelope glycoprotein purified from CrFK-tropic virus competed specifically for binding of SDF-1alpha to feline CXCR4 and CXCR4 expression was reduced in FIV-infected cells, suggesting that the inhibitory activity of SDF-1alpha in CrFK cells may be the result of steric hindrance of the virus-receptor interaction following the interaction between SDF and CXCR4. Prolonged incubation of CrFK cells with SDF-1alpha led to an enhancement rather than an inhibition of infection. Flow cytometric analysis revealed that this effect may be due largely to up-regulation of CXCR4 expression by SDF-1alpha on CrFK cells, an effect mimicked by treatment of the cells with phorbol myristate acetate. The data suggest that infection of feline cells with FIV can be mediated by CXCR4 and that, depending on the assay conditions, infection can be either inhibited or enhanced by SDF-1alpha. Infection with FIV may therefore prove a valuable model in which to study the development of novel therapeutic interventions for the treatment of AIDS.
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PMID:Modulation of feline immunodeficiency virus infection by stromal cell-derived factor. 949 65

Infection with the Epstein-Barr virus (EBV) is common worldwide. A significant number of infected individuals develop infectious mononucleosis (IM). IM is manifested in most patients as a benign disease with mild symptoms. However, serious complications may develop in a subset of patients. Because EBV-infected B lymphocytes produce various cytokines that may provide the cells with a proliferative advantage, cytokine concentrations in serum samples taken from IM patients were measured in order to identify the cytokines responsible for the clinical manifestations of the disease. The concentrations of interleukin-1beta (IL-1beta), IL-2, IL-6, IL-8, IL-10, tumor necrosis factor-alpha (TNF-alpha), and lymphotoxin (LT) were measured using an enzyme-linked immunosorbent assay (ELISA) in serum obtained from 14 IM patients during the acute phase of the disease and during convalescence, 5 patients with identical clinical manifestations who did not have IM (sick controls), and 11 healthy volunteers. It was found that the serum levels of TNF-alpha and IL-6 were significantly high in patients with acute IM compared with the serum levels in healthy individuals (P = 0.008 and P < 0.001, respectively) but returned to normal at convalescence (P = 0.009 and P = 0.005 respectively). However, whereas TNF-alpha concentrations were significantly higher (P = 0.04) in patients with acute IM than in the sick controls, no significant difference in IL-6 concentrations was found between the two groups of patients. Changes in IL-10 concentration were not statistically significant, and IL-1beta, IL-2, IL-8, and LT were detected only sporadically. The data in this study suggest that TNF-alpha may have a specific role in causing the clinical manifestations of IM. Further studies should determine the clinical significance of TNF-alpha inhibition in IM.
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PMID:Serum cytokine levels in infectious mononucleosis at diagnosis and convalescence. 971 20

A prospective study was performed to assess the potential value of interleukin (IL)-8, IL-6, and C-reactive protein (CRP) serum levels to predict fever, gram-negative bacteremia and complicated infection in neutropenic patients with cancer. Serum samples were obtained three times a week during 208 neutropenic episodes following cytotoxic chemotherapy. Fever of any cause developed during 104 out of 191 evaluable episodes. Serum levels of neither cytokine nor CRP were predictive of fever within more than 24 h before its onset. Unlike CRP, both IL-6 and IL-8 serum levels were significantly different between microbiologically documented infections and unexplained fevers. The highest values of IL-6 and IL-8 were observed in episodes of gram-negative bacteremia. Using receiver-operating-characteristic curves, the analysis of cytokine levels measured around the onset of fever indicated that IL-8 is potentially useful for predicting gram-negative bacteremia, with a high negative predictive value of > 90% and a moderate positive predictive value of 50% (sensitivity, 70%; specificity, 91%). In patients with persistent fever, predictions of further clinical complications, defined as prolonged fever of more than 7 days' duration, pneumonia, shock and/or death due to infection, were best predicted by IL-6. With an IL-6 cutoff value of 250 pg/ml in samples obtained 8 to 32 h after onset of fever, the positive predictive value was 92%, the negative predictive value 91% (sensitivity, 85%; specificity, 95%). The positive predictive value of IL-6 in samples obtained another 24 h later from patients still febrile remained > 90%, but the negative predictive value dropped to 47%. In any of the analyses, the predictive values of CRP levels were poor and inferior to either cytokine. These findings may have clinical value in identifying subgroups of patients requiring different therapeutic approaches.
Infection
PMID:An analysis of interleukin-8, interleukin-6 and C-reactive protein serum concentrations to predict fever, gram-negative bacteremia and complicated infection in neutropenic cancer patients. 971 78

Infection by Helicobacter pylori, a noninvasive bacterium, induces chronic leukocyte infiltration in the stomach by still largely unknown molecular mechanisms. We investigated the possibility that a membrane protein of H. pylori induces an inflammatory reaction in the subepithelial tissue of the stomach. By generating an expression library of H. pylori chromosomal DNA and screening with rabbit antiserum raised to a membrane fraction of H. pylori and sera of infected patients, we cloned a 16.0-kDa protein (HP-MP1) which appeared to attach to the inner membrane of the H. pylori in a homodimeric form. Anti-HP-MP1 antibodies were detected in the sera of infected patients but not in those of uninfected controls. Coincubation of monocytes with recombinant HP-MP1 led to cell activation and production of interleukin-1alpha (IL-1alpha), tumor necrosis factor alpha, IL-8, and macrophage inflammatory protein 1alpha. The results indicate that HP-MP1 is an antigenic membrane-associated protein of H. pylori which potentially activates monocytes. This suggests that HP-MP1 may play roles in the pathogenesis of perpetual tissue inflammation associated with H. pylori infection.
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PMID:Cloning and characterization of a novel membrane-associated antigenic protein of Helicobacter pylori. 986 28

A large number of clinical studies has described procalcitonin (ProCT) as a marker of bacterial infection and a good predictor of disease severity and antibiotherapy efficacy. Nevertheless, the mechanism of ProCT synthesis remains unclear. The aim of this study was to demonstrate potential ProCT production by peripheral blood mononuclear cells as is the case for cytokines involved in sepsis. In a whole blood model, LPS (10 micrograms/ml) stimulation on blood samples from healthy volunteers (n = 14) was tested. Early (TNF-alpha and IL1-beta) and late (IL-6 and IL-8) cytokines were produced in large amounts in contrast to the absence of ProCT. Additional experiments with nitric oxide or detection of intra-cellular ProCT (cell lysis, flow cytometry) had negative results. It was concluded that ProCT is not produced in this model. Data are still needed to investigate the cellular origin of ProCT in order to better define its clinical usefulness.
Infection
PMID:Procalcitonin is not produced by circulating blood cells. 1002 4

This study examined the role of P and type 1 fimbriae for neutrophil migration across Escherichia coli-infected uroepithelial cell layers in vitro and for neutrophil recruitment to the urinary tract in vivo. Recombinant E. coli K-12 strains differing in P or type 1 fimbrial expression were used to infect confluent epithelial layers on the underside of transwell inserts. Neutrophils were added to the upper well, and their passage across the epithelial cell layers was quantified. Infection with the P- and type 1-fimbriated recombinant E. coli strains stimulated neutrophil migration to the same extent as a fully virulent clinical E. coli isolate, but the isogenic non-fimbriated vector control strains had no stimulatory effect. The enhancement of neutrophil migration was adhesion dependent; it was inhibited by soluble receptor analogues blocking the binding of P fimbriae to the globoseries of glycosphingolipids or of type 1 fimbriae to mannosylated glycoprotein receptors. P- and type 1-fimbriated E. coli triggered higher interleukin (IL) 8 secretion and expression of functional IL-8 receptors than non-fimbriated controls, and the increase in neutrophil migration across infected cell layers was inhibited by anti-IL-8 antibodies. In a mouse infection model, P- or type 1-fimbriated E. coli stimulated higher chemokine (MIP-2) and neutrophil responses than the non-fimbriated vector controls. The results demonstrated that transformation with the pap or fim DNA sequences is sufficient to convert an E. coli K-12 strain to a host response inducer, and that fimbriation enhances neutrophil recruitment in vitro and in vivo. Epithelial chemokine production provides a molecular link between the fimbriated bacteria that adhere to epithelial cells and tissue inflammation.
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PMID:Role of fimbriae-mediated adherence for neutrophil migration across Escherichia coli-infected epithelial cell layers. 1009 21


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