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)

Volatile organic compounds (VOCs) have been implicated as causative agents in asthma and building-related illness. To determine whether a mixture of VOCs could impair lung function or cause airway inflammation among subjects without bronchial hyperresponsiveness, the authors conducted a randomized, crossover-design trial of controlled human exposures to filtered air for four hours, VOCs at 25 mg/m(3) for four hours, and VOCs at 50 mg/m(3) for four hours, using a VOC mixture based on sampling of indoor environments. VOC exposures caused dose-related increases in lower respiratory, upper respiratory, and non-respiratory symptoms, with no significant change in lung function (FEV(1);, FVC, or FEF(25-75), nasal lavage cellularity or differential cell counts, induced sputum cellularity or differential cell counts, or biomarkers of airway inflammation, including IL-8, LTB(4), or albumin in nasal lavage or induced sputum samples. Atopic individuals had significantly reduced FEE(25-75 following exposure to VOCs at 50 mg/m(3), suggesting that these individuals may be more sensitive to the health effects of VOCs. The authors conclude that reductions in levels of VOCs to substantially less than 25 mg/m(3) are required if a "non-irritating" work environment is desired.
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PMID:The respiratory effects of volatile organic compounds. 1063 31

Assessment of disease activity in inflammatory bowel disease (IBD), i.e., ulcerative colitis (UC) and Crohn's disease (CD), is done using clinical parameters and various biological disease markers. Ideally, a disease marker must: be able to identify individuals at risk of a given disorder, be disease specific, mirror the disease activity and, finally, be easily applicable for routine clinical purposes. However, no such disease markers have yet been identified for IBD. In this article, classical disease markers including erythrocyte sedimentation rate, acute phase proteins (especially orosomucoid and CRP), leukocyte and platelet counts, albumin, neopterin, and beta2-microglobulin will be reviewed together with emerging disease markers such as antibodies of the ANCA/ASCA type, cytokines (e.g., IL-1, IL-2Ralpha, IL-6, IL-8, TNF-alpha, and TNF-alpha receptors) and with various adhesion molecules. It is concluded that none of the pertinent laboratory surrogate markers of disease activity in IBD are specific or sensitive enough to replace basic clinical observation such as the number of daily bowel movements, general well-being, and other parameters in parallel. Further studies are highly warranted to identify and assess the clinical importance and applicability of new laboratory markers for the diagnosis or the disease activity of IBD.
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PMID:Established and emerging biological activity markers of inflammatory bowel disease. 1092 11

Tryptase, the major product of human mast cell activation, is a potent stimulus of vascular leakage and neutrophil accumulation in vivo in animal studies, but the mechanisms of action remain unclear. Using HUVEC cultures we have sought to investigate the potential of tryptase to alter monolayer permeability or induce the release of neutrophil chemotactic activity. Tryptase (1-100 mU/ml) failed to alter the permeability of endothelial cell monolayers as assessed by albumin flux over 1 h. However, supernatants from endothelial cells treated with tryptase (1-50 mU/ml) for a 24-h period induced neutrophil migration across Transwell filters, with maximal migration observed at 10 mU/ml tryptase. Pretreatment of tryptase with the protease inhibitor leupeptin abolished the chemotactic activity, indicating a dependence on the catalytic site. Moreover, this effect was abolished by addition of an IL-8 neutralizing antibody, suggesting that IL-8 release makes an important contribution to the chemotactic activity. The interaction of mast cell tryptase with endothelial cells could be important in stimulating the ingress of neutrophils following mast cell activation in inflammatory disease.
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PMID:Human mast cell tryptase stimulates the release of an IL-8-dependent neutrophil chemotactic activity from human umbilical vein endothelial cells (HUVEC). 1088 36

The aim of this study was to assess the cytokine response after nasal exposure to organic dusts. In a double blinded, crossover study five garbage workers with occupational airway symptoms and five healthy garbage workers were intranasally exposed to endotoxin (lipopolysaccharide LPS), beta-1,3-D-glucan (GLU), Aspergillus sp., compost or the saline dilute for 15 min. Nasal cavity volume and nasal lavage (NAL) were performed at baseline and 3, 6, 11 h postexposure. NAL was analysed with differential cell counts, cysteinyl-leukotrienes, tumour necrosis factor alpha, interleukin (IL)-1beta, IL-6 and IL-8. A whole blood assay on cytokine-release was performed with LPS and GLU. NAL cytokines neutrophils, lymphocytes and albumin increased significantly at 6 h after LPS exposure. GLU induced an increase in albumin and a slight increase in IL-1beta 6-11 h post exposure. In the WBA a significant increase in all cytokines after exposure to LPS as well as GLU was found. Significantly more cells were seen in NAL of the control group 6 h post LPS exposure. In conclusion lipopolysaccharide is the most potent inducer of inflammation in the nasal mucosa whereas compost and beta-1,3-D-glucan only induce minor changes. This reaction to lipopolysaccharide is attenuated in workers with occupational airway symptoms. In whole blood assay, however, beta-1,3-D-glucan also induces cytokine release, indicating a different protective effect of the nasal mucosa towards lipopolysaccharide and beta-1,3-D-glucan.
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PMID:Cytokine release from the nasal mucosa and whole blood after experimental exposures to organic dusts. 1093

These pieces of evidence can be assimilated into a molecular and cellular model of pathogenesis which is initiated by direct toxin effects upon venous capillary endothelial cell function, leading to expression of pro-inflammatory mediators and adhesion molecules, and initiation of platelet aggregation. Toxin-induced hyperadhesion of leukocytes (see above section) with enhanced respiratory burst activity (due to toxins directly or to toxin-induced IL-8 or PAF synthesis by host cells) and toxin-induced chemotaxis deficits could result in neutrophil-mediated vascular injury. Direct toxin-induced cytopathic effects on EC may also contribute to vascular abnormalities associated with gas gangrene. Over prolonged incubation periods, PLC at sublytic concentrations causes EC to undergo profound shape changes similar to those described following prolonged TNF or interferon gamma exposure. In vivo, conversion of EC to this fibroblastoid morphology could contribute to the localized vascular leakage and massive swelling observed clinically with this infection. Similarly, the direct cytotoxicity of PFO could disrupt endothelial integrity and contribute to progressive edema both locally and systemically. Thus, via the mechanisms outlined above, both PLC and PFO may cause local, regional and systemic vascular dysfunction. For instance, local absorption of exotoxins within the capillary beds could affect the physiological function of the endothelium lining the postcapillary venules, resulting in impairment of phagocyte delivery at the site of infection. Toxin-induced endothelial dysfunction and microvascular injury could also cause loss of albumin, electrolytes, and water into the interstitial space resulting in marked localized edema. These events, combined with intravascular platelet aggregation and leukostasis, would increase venous pressures and favor further loss of fluid and protein in the distal capillary bed. Ultimately, a reduced arteriolar flow would impair oxygen delivery thereby attenuating phagocyte oxidative killing and facilitating anaerobic glycolysis of muscle tissue. The resultant drop in tissue pH, together with reduced oxygen tension, might further decrease the redox potential of viable tissues to a point suitable for growth of this anaerobic bacillus. As infection progresses and additional toxin is absorbed, larger venous channels would become affected, causing regional vascular compromise, increased compartment pressures and rapid anoxic necrosis of large muscle groups. When toxins reach arterial circulation, systemic shock and multiorgan failure rapidly ensue, and death is common.
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PMID:The pathogenesis of clostridial myonecrosis. 1111 33

Pseudomonas aeruginosa infection frequently complicates lung injury and can be fatal in immunocompromised or debilitated individuals. Previous studies from our laboratory indicate that elastase from P. aeruginosa increases epithelial permeability by disrupting tight junctions between epithelial cells. Because the inflammatory reaction of the host is a prominent feature of bacterial infection, we reasoned that additional virulence factors from this organism could extend and augment the initial pulmonary injury by prompting accumulation of neutrophils. To test this hypothesis, we compared responses of guinea pigs to aerosols of elastase (PE) and lipopolysaccharide (LPS) from P. aeruginosa. After each treatment, we measured epithelial permeability and accumulation of neutrophils, interleukin 8 (IL-8), and beta-glucuronidase in epithelial lining fluid (ELF). We found that PE increased epithelial permeability, as measured by both the clearance of aerosolized radiolabeled albumin from the air spaces and the concentration of plasma albumin in epithelial lining fluid, but it was less effective than LPS at recruiting neutrophils into the lungs. In contrast, LPS had no significant effect on epithelium, but it increased the concentration of neutrophils, IL-8, and beta-glucuronidase in ELF. Increased epithelial permeability induced by PE does not cause lung inflammation, but it may facilitate the LPS-induced influx of neutrophils.
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PMID:Virulence factors from Pseudomonas aeruginosa increase lung epithelial permeability. 1114 11

The aim of this study was to monitor hepatic function in patients with pneumonia meeting the sepsis criteria of the American College of Chest Physicians/Society of Critical Care Medicine (ACCP/SCCM) and to determine if hepatic dysfunction is related to the systemic inflammatory response. Twenty patients were recruited. The monoethylglycinexylidide (MEGX) test was carried out on days 1-10 after admittance to the intensive care unit. Blood samples for determination of serum concentrations of hyaluronic acid, C-reactive protein (CRP), interleukin (IL)-6, IL-8, IL-10 and conventional liver function tests (aspartate aminotransferase, alanine aminotransferase, bilirubin, albumin) were also drawn. Patients were classified into two groups according to illness severity estimated by the simplified acute physiology score (SAPS II) on the day of admission. Patients in group I (n=10) had a SAPS II probability of mortality >3% while those in group II (n=10) had a SAPS II < 3%. The MEGX level over the first five days was significantly lower in group I than in group II (p<0.0001). Significant inverse correlations during the first 5 days were observed between the MEGX 30 min test results and IL-6, CRP and SAPS II and more modest correlations with hyaluronic acid (p=0.0025) and IL-10 (p=0.021). The conventional liver function tests did not differ between the two groups and were mostly within the respective reference ranges. We conclude that the MEGX test is a sensitive marker of liver dysfunction early in sepsis and that low MEGX values are associated with an enhanced inflammatory response.
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PMID:The monoethylglycinexylidide (MEGX) test as a marker of hepatic dysfunction in septic patients with pneumonia. 1115 41

Information on the dose-response relationship is a prerequisite to defining the non-response threshold of exposure. We investigated whether nasal lipopolysaccharide (LPS) challenges induce an inflammatory response in a dose-dependent way. In three settings nasal lavage was performed before, and 20 min, 1, 6, 23, and 29 h after instillation of 0 microg, 10 microg, and 40 microg LPS for 10 s, in seven healthy subjects. Lavage fluids were analysed for concentrations of interleukin-6 (IL-6), IL-8, tumour necrosis factor-alpha (TNF-alpha), histamine, and albumin. Symptoms were recorded by questionnaire and spirometric lung function was assessed after each lavage. The instillation of 40 microg LPS caused a small increase in nasal symptoms. TNF-alpha was below the detection limit (0.5 pg/ml) in most subjects and, like IL-8 and albumin, showed no relation to the LPS challenge. IL-6 increased over twofold with 10 microg LPS and over 13-fold with 40 microg LPS, with a peak at 6 h after LPS provocation, and the repeated design ANOVA was significant for dose and for time. Six hours after the 40 microg LPS challenge the histamine level significantly increased compared to the saline treatment. We conclude that short-lasting instillation of LPS causes a dose-dependent IL-6 release in the upper airways and minor nasal symptoms.
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PMID:Lipopolysaccharide-induced nasal cytokine response: a dose-response evaluation. 1119 30

We examined the influence of atopy on virus-induced airway inflammation by comparing the nasal response to naturally acquired upper respiratory tract infection in atopic and nonatopic subjects by measurement of cytokine, chemokine, and mediator levels in nasal lavage from 44 adults (23 atopic) taken during the acute and the convalescent phases of the common cold. Nasal aspirates were examined for the presence of upper respiratory viruses by RT-PCR. In atopic and nonatopic subjects there were increased levels of IL-1beta, IL-6, IL-8, TNF-alpha, RANTES, sICAM-1, MPO, ECP, IL-10, and IFN-gamma in nasal lavage during the acute compared with the convalescent phase (p < 0.001). During the acute phase histamine levels were significantly higher in the atopic than in the nonatopic subjects (p < 0.05), whereas IL-10 levels were significantly greater in the nonatopic than in the atopic subjects (p < 0.05). At convalescence levels of IL-1beta, IL-6, sICAM-1, ECP, RANTES and albumin were significantly higher in the atopic group (p < 0.05). An upper respiratory tract virus was found in 27 volunteers (61%) during the acute stage and in two volunteers (4%) at convalescence. We conclude that virus-induced inflammatory changes within the nose are more prolonged in atopic than in nonatopic subjects and that this is associated with reduced IL-10 levels in atopic compared with nonatopic subjects during the acute phase of upper respiratory tract infection.
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PMID:The relationship between atopic status and IL-10 nasal lavage levels in the acute and persistent inflammatory response to upper respiratory tract infection. 1131 43

To study local lung inflammation, 34 subjects had endotoxin (1-4 ng/kg) instilled into a lung segment and saline instilled into a contralateral segment followed by bronchoalveolar lavage (BAL) at 2 h, 6 h, 24 h, or 48 h. Endotoxin instillation resulted in a focal inflammatory response with a distinct time course. An early phase (2 h to 6 h) revealed an increase in neutrophils (p = 0.0001) with elevated cytokines (tumor necrosis factor [TNF]-alpha, TNF receptors [TNFR], interleukin [IL]-1beta, IL-1 receptor antagonist, IL-6, granulocyte-colony-stimulating factor [G-CSF], all p < or = 0.002, but no change in IL-10) and chemokines (IL-8, epithelial neutrophil activating protein-78, monocyte chemotactic protein-1, macrophage inflammatory protein [MIP]-1alpha, MIP-1beta, all p < or = 0.001, but no change in growth-regulated peptide-alpha). A later phase (24 h to 48 h) showed increased neutrophils, macrophages, monocytes, and lymphocytes (all p < or = 0.02), and a return to basal levels of most mediators. Elevated levels of inflammatory markers (TNFR(1), TNFR(2), L-selectin, lactoferrin, and myeloperoxidase) persisted in the BAL at 48 h (p < or = 0.001). Increased permeability to albumin occurred throughout both phases (p = 0.001). Blood C-reactive protein, serum amyloid A, IL-6, IL-1ra, G-CSF, but not TNF-alpha increased by 8 h (all p < or = 0.008). The local pulmonary inflammatory response to endotoxin has a unique qualitative and temporal profile of inflammation compared with previous reports of intravenous endotoxin challenges. This model provides a means to investigate factors that initiate, amplify, and resolve local lung inflammation.
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PMID:Local inflammatory responses following bronchial endotoxin instillation in humans. 1140 64


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