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)

Pro- and antiinflammatory cytokines and mediators were measured in 39 patients with acute life-threatening meningococcal infections classified into 3 groups: A, meningitis without shock (n = 20); B, meningitis with shock (n = 9); and C, shock without meningitis (n = 10). The plasma concentrations of proinflammatory endotoxin, tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, and IL-8 and antiinflammatory cytokines and mediators IL-1 receptor antagonist, IL-10, and soluble TNF receptors p55 and p75 were strongly associated with this classification; the highest concentrations were in group C. IL-4 was not measurable. IL-1 beta was increased only in rapidly fatal cases. In addition, cerebrospinal fluid (CSF) was analyzed in 21 patients for TNF-alpha and its soluble receptors. In CSF, these compounds were mainly increased in group A, reflecting an intrathecal compartmentalized cytokine production. It is concluded that both pro- and antiinflammatory mediators are simultaneously increased and are strongly associated with a classification based on simple clinical parameters.
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PMID:Correlation between proinflammatory cytokines and antiinflammatory mediators and the severity of disease in meningococcal infections. 762 86

Septic shock following gram-negative infection is a leading cause of mortality in critically ill patients, accounting for nearly 200,000 deaths a year. The exaggerated production of tumor necrosis factor-alpha (TNF alpha) is known to contribute to hemodynamic collapse and the hematological dyscrasia associated with gram-negative sepsis. Although previous studies have shown TNF alpha antibodies and TNF immunoadhesins to be effective in experimental gram-negative sepsis, we postulated that administration of a novel construct of two modified soluble p55 receptors linked to polyethylene glycol (PEG-BP-30) would also attenuate the hemodynamic and hematologic alterations to lethal Escherichia coli septic shock in non-human primates. Nine adult female and male baboons (Papio anubis), weighing 10-17 kg, were anesthetized and invasively monitored. The nine animals were randomized to receive either 0.2 mg/kg body wt PEG-BP-30 (n = 3), 5.0 mg/kg body wt PEG-BP-30 (n = 3), or placebo (n = 3). One hour after pretreatment, animals were infused with 5-10 x 10(10) CFU/kg of live E. coli iv and vital signs were recorded for the next 8 hr. Arterial blood was drawn for baseline parameters and throughout the study to obtain total and differential white blood cell and platelet counts and cytokine levels (TNF alpha, IL-1 beta, IL-6, IL-8). E. coli bacteremic baboons receiving only placebo demonstrated a significant fall in mean blood pressure and leukopenia. Two of the three animals expired. In contrast, five of the six baboons receiving the PEG-BP-30 survived and these animals exhibited markedly attenuated declines in blood pressure and leukocyte numbers.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:PEG-BP-30 monotherapy attenuates the cytokine-mediated inflammatory cascade in baboon Escherichia coli septic shock. 763 Jan 20

The administration of a high-dose of a serine protease inhibitor is recommended in patients complicated by multiple organ failure (MOF), including adult respiratory distress syndrome (ARDS), induced by acute pancreatitis. The accumulation of polymorphonuclear leukocytes (PMN) in affected organs is considered to be one of the causative factors of MOF. Adhesion to endothelial cells (EC), via adhesion molecules, and the transendothelial migration of PMN is closely associated with the accumulation of PMN. We examined the effects of two serine protease inhibitors, ulinastatin (UT) and gabexate mesilate (GM), on EC-PMN adhesion and transendothelial migration in human umbilical vein EC and 51Cr-labeled PMN in vitro. EC-PMN adhesion, and the expression of intercellular adhesion molecule-1 (ICAM-1) and endothelial cell adhesion molecule-1 (ELAM-1) on EC induced by IL-1 beta and TNF alpha, were reduced by the pretreatment of EC with these inhibitors. The transendothelial migration of PMN stimulated by IL-8 was also inhibited by pretreating PMN with UT or GM. We also examined whether these inhibitors reduced PMN accumulation in the lung in rats with acute pancreatitis induced by a closed duodenal loop. The myeloperoxidase activity in and histological findings of the lung suggested that UT and GM reduced PMN accumulation. In conclusion, serine protease inhibitors may inhibit PMN accumulation in ARDS due to acute pancreatitis.
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PMID:Effects of serine protease inhibitors on accumulation of polymorphonuclear leukocytes in the lung induced by acute pancreatitis in rats. 764 5

The multiorgan failure syndrome caused by group A streptococci (GAS) designated streptococcal toxic shock syndrome (STSS) is believed to be mediated by cytokines induced by superantigens. In order to study the relationship between superantigen production, cytokine levels in patient sera, and clinical GAS manifestation we examined acute-phase sera and strains from 25 patients with GAS bacteremia. The patients had various disease manifestations, including STSS (44%), erysipelas (28%), septicemia (24%), wound infections (16%), and pneumonia (12%). Serotype T1M1 dominated, representing 56% of the isolates, but also strains of other serotypes were identified. The strains were found to produce the streptococcal pyrogenic exotoxins (Spe) A, B, and F, as determined by immuno-blot analyses. There was no difference in amounts of toxin produced between strains isolated from patients with different manifestations of disease. Levels of TNF alpha, IL1 alpha, IL6, IL8, and IFN gamma in acute-phase sera were determined by use of ELISA and RIA assays. The analyses showed higher levels of IL6 in sera from patients with STSS than in sera from patients with bacteremia without shock. TNF alpha was elevated in sera from patients with STSS, as compared to sera from patients with uncomplicated pharyngotonsillitis. No increase in the levels of IL1 alpha, IL8, and IFN gamma could be found in the patient sera and there was no difference in the level of those cytokines between the various patient categories.
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PMID:Correlation between serum TNF alpha and IL6 levels and severity of group A streptococcal infections. 766 74

Interleukin-8 (IL-8) is a major neutrophil chemoattractant and functional stimulant that is induced by IL-1, tumor necrosis factor alpha (TNF alpha), and lipopolysaccharide (LPS). We report that recombinant human (rh) granulocyte-macrophage colony-stimulating factor (GM-CSF) and rhIL-3 are also potent inducers of IL-8 messenger RNA (mRNA) accumulation and protein secretion by normal peripheral blood monocytes. Neutrophils produce IL-8 in response to GM-CSF but not to IL-3. In contrast, recombinant human granulocyte-CSF (rhG-CSF), at concentrations as high as 100 ng/mL, does not induce IL-8 in either cell type. rhGM-CSF also induces IL-8 mRNA expression and IL-8 protein in the promonocytic cell line, U-937, whereas rhG-CSF does not. IL-8 secretion by monocytes was stimulated within 2 hours after incubation with rhGM-CSF or rhIL-3. Stimulation of neutrophils with rhGM-CSF resulted in an increase in cell-associated IL-8 at 4 hours. At 24 hours, cell-associated IL-8 levels declined, whereas secreted IL-8 levels increased. In contrast, virtually all IL-8 induced in monocytes appeared as secreted protein. Neither rhGM-CSF nor rhIL-3 induced detectable secretion of IL-1, TNF alpha, or IL-6 protein by monocytes. rhGM-CSF, and to a lesser degree rhIL-3, potently stimulated IL-8 secretion in cultures of heparinized whole blood, whereas rhG-CSF had no significant effect on IL-8 secretion. Induction of IL-8 by GM-CSF may be physiologically important in enhancing the acute inflammatory response.
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PMID:Effect of granulocyte-macrophage colony-stimulating factor and interleukin-3 on interleukin-8 production by human neutrophils and monocytes. 767 12

Children undergoing cardiopulmonary bypass (CPB) surgery for congenital heart defects develop an acute post-operative capillary leak which may be due to endothelial injury inflicted by adherent neutrophils (PMN). Direct immunofluorescence and flow cytometry were used to measure CD11a/CD18, CD11b/CD18 and L-selectin (L-s) expression on circulating PMN in CPB circuits containing human blood and in children undergoing CPB. In vitro, a general rise in CD11b/CD18 expression over 2 h contrasted with complete loss of L-s in a small but progressively increasing proportion of PMN. Marked but inconsistent changes in CD11b/CD18 and L-s were observed in vivo, in conjunction with fluctuations in circulating PMN count. Circulating IL-8 was detected starting at rewarming from hypothermia and reperfusion of the heart and lungs with a simultaneous, closely correlated rise in both PMN count and circulating elastase. IL-1 and TNF were not detected. These studies demonstrate changes in the pathways of PMN-endothelial interaction during and after CPB.
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PMID:Changes in neutrophil CD11b/CD18 and L-selectin expression and release of interleukin 8 and elastase in paediatric cardiopulmonary bypass. 768 23

Phagocytosis of Mycobacterium tuberculosis by human monocytes or macrophages is classically followed by granuloma formation in vivo. Granuloma are comprised of cells of the monocyte lineage together, in many instances, with antigen-specific T lymphocytes. Development of granuloma depends upon recruitment of both cell types, but recruitment of monocytes is pivotal as these cells secrete anti-mycobacterial cytokines and IL-8, a T cell chemoattractant. We have therefore investigated gene regulation of Monocyte Chemotactic Protein 1 (MCP-1), an important monocyte chemotactic cytokine, following phagocytosis of particulate material (latex beads and zymosan) and live M. tuberculosis by two human monocytic cell lines. In THP-1 cells and phenotypically more differentiated Mono Mac 6 cells, MCP-1 mRNA accumulation was first detectable by Northern analysis of 4 hours and increased over 24 hours. Magnitude and kinetics of MCP-1 gene expression was independent of the biochemical nature of the phagocytic stimulus, M. tuberculosis strain virulence or pre-treatment with anti-TNF. In contrast to the uniform effect of different phagocytic stimuli on MCP-1 gene expression, we have shown that M. tuberculosis but not latex or zymosan, increased IL-8 gene expression, a chemotactic agent for T cells. In additional experiments with THP-1 cells infected with human immunodeficiency virus (HIV), viral infection did not alter MCP-1 gene expression following phagocytosis. MCP-1 gene expression appears to be a conserved antigen-independent response of human monocytic cells which is activated following particulate phagocytosis. MCP-1 gene expression may thus be involved in recruitment of monocytes during granuloma formation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phagocytosis of Mycobacterium tuberculosis or particulate stimuli by human monocytic cells induces equivalent monocyte chemotactic protein-1 gene expression. 768 73

Pulmonary fibrosis corresponds to an accumulation of collagens and other proteins of the extracellular matrix in the interstitium and alveoli. Biochemical and cellular mechanisms of pulmonary fibrogenesis remain poorly understood. The cells of the alveolitis (macrophages, lymphocytes and neutrophils) play a key role in producing the factors which regulate the proliferation, chemotactism and secretory activity of the fibroblasts. Amongst these factors the cytokines (interleukins, interferons and growth factors) play a definite but very complex role. Certain cytokines stimulate in vitro the attraction and activation of cells of the alveolitis, as well as the multiplication, migration and secretory activity of fibroblasts. The following cytokines are involved: tumour necrosis factor alpha: (TNF alpha), interleukin 1 (IL-1), interleukin 6 (IL-6) interleukin 8 (IL-8) transforming growth factor beta (TGF beta), platelet derived growth factor (PDGF), insulin like growth factor 1 (IGF-1), fibronectin, monocyte chemotactic protein 1: (MCP-1). Other cytokines, principally the interferons (of alpha, beta or gamma type: IFN alpha, IFN beta, IFN gamma) inhibit in vitro and in vivo the proliferation and the production of collagen by fibroblasts. During the course of human pulmonary fibrosis or in experimental situations, the majority of the cytokines mentioned above are produced in excess in the lung. Without doubt they play an important role in the pathogenesis of fibrosis, even if it is not yet very well known how they interact and contribute in vitro to the process of fibrogenesis. Certain cytokines potentially regulating in the fibrosis are yet to be identified. In the future the use of cytokines and of their inhibitors will perhaps provide new therapies in pulmonary fibrosis.
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PMID:[Cytokines and pulmonary fibroses]. 768 79

According to the type of secondary structure, cytokines are classified into three categories: alpha-spiral (IFNs-alpha, beta, omega, gamma; ILS-2, 3,4,5,6,7,9; CSFs-G, M, GM, MGF, PDGF), beta-structural (ILs-1 alpha, beta, TNFs-alpha, beta, FGF) and (alpha + beta)-structural proteins (IL-8, IFN-gamma IP-10, PF-4, bTG, GRO, 9E3). According to the type of tertiary structure, alpha-spiral proteins are grouped into IFN- and IL-2-like families and beta-structural ones into IL-1-, and TNF-like families. Two subfamilies can be identified in the IFN-like family. Theoretical and experimental evidence suggests that the genes IFNs are products of divergent or convergent evolution towards the gene of the ancient intracellular protein alpha-prothymosine, which is evolutionally in turn associated with the L7/I1 protein of two ribosomes. It is suggested that the proteins of the immunoglobulin superfamily, including cytokine receptors descended from the ancient proteins of the unicellular organisms molecular shaperons.
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PMID:[The structural and functional classification and evolution of cytokines]. 768 23

Cystic fibrosis (CF) is characterized by a dramatic neutrophil recruitment and repeated Pseudomonas infections in the lungs. To evaluate cytokine releasibility by airway epithelial cells in the context of CF, we studied primary nasal epithelial cells isolated from the upper airways and continuous epithelial cell lines from normal and CF subjects. Relatively low levels of interleukin (IL)-8, IL-6, and granulocyte/macrophage colony-stimulating factor (GM-CSF) were produced spontaneously by primary epithelial cells (< 50 pg/10(6) cells) and higher levels of colony-stimulating factor-1 (CSF-1) (1 to 2 ng/10(6) cells). Cells were stimulated with substances that are likely to be present in the inflamed lungs of CF patients-namely, the proinflammatory monokines IL-1 and tumor necrosis factor-alpha (TNF alpha) as well as neutrophil elastase and bacterial products from Pseudomonas (mucoid exopolysaccharide [MEP] and rhamnolipids). Both IL-1 and TNF alpha induced a dose-dependent release of IL-6 (5 to 10 ng/10(6) cells) and GM-CSF (2 to 3 ng/10(6) cells) by primary epithelial cells from eight normal volunteers. The TNF alpha/IL-1-stimulated GM-CSF release was blocked by the addition of 1 microM dexamethasone, whereas basal CSF-1 release was unaffected. Neutrophil elastase was a potent inducer of IL-8 and GM-CSF both in primary epithelial cells and in cell lines. Dexamethasone (1 microM) did not inhibit elastase-induced IL-8 release in either normal or CF epithelial cells. Rhamnolipids and MEP were found to stimulate the copious release of IL-8, GM-CSF, and IL-6 from epithelial cells, in a steroid-sensitive fashion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Release of interleukin-8, interleukin-6, and colony-stimulating factors by upper airway epithelial cells: implications for cystic fibrosis. 769 Nov 10


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