interleukin-8 and Respiratory-Tract-Diseases

Since the discovery of IL-17 in 1995 as a T-cell cytokine, inducing IL-6 and IL-8 production by fibroblasts, and the report of a separate T-cell lineage producing IL-17(A), called Th17 cells, in 2005, the role of IL-17 has been studied in several inflammatory diseases. By inducing IL-8 production and subsequent neutrophil attraction towards the site of inflammation, IL-17A can link adaptive and innate immune responses. More specifically, its role in respiratory diseases has intensively been investigated. We here review its role in human respiratory diseases and try to unravel the question whether IL-17A only provides a link between the adaptive and innate respiratory immunity or whether this cytokine might also be locally produced by innate immune cells. We furthermore briefly discuss the possibility to reduce local IL-17A production as a treatment option for respiratory diseases.

Topics: Adaptive Immunity; Animals; Biomedical Research; Humans; Immunity, Innate; Immunotherapy; Interleukin-17; Interleukin-8; Molecular Targeted Therapy; Neutrophil Activation; Respiratory Tract Diseases; T-Lymphocytes, Helper-Inducer

This paper's goal is to review the relationship between infections and chronic respiratory disease, with particular reference to periodontal disease. The link between oral diseases in general, periodontal disease, and respiratory disease remains somewhat controversial. However, with cooperation between dentistry and medicine, the nature of the connection between dental and medical pathology can be better defined. An overview of respiratory disease and some of the factors that can contribute to respiratory infection is presented below, with special reference to infections related to aspiration.

Topics: Bacteria; Cough; Deglutition; Humans; Interleukin-8; Lung; Periodontal Diseases; Pneumonia, Aspiration; Pneumonia, Bacterial; Pulmonary Disease, Chronic Obstructive; Respiratory Physiological Phenomena; Respiratory Tract Diseases; Respiratory Tract Infections; Risk Factors; Saliva; Smoking

In rooms with moisture damage, the indoor air can be enriched with microorganisms causing a variety of symptoms. Due to the highly diverse composition of bioaerosols and the multiple effects on humans, an assessment of the health risk is not sufficiently possible. The aim of this study was to characterize the features of innate immunity using blood from subjects exposed to moisture damage compared to control subjects living in houses without visible moisture damage. We investigated the expression of TLR-2, TLR-4 and dectin-1 on the surface of monocytes from both fresh blood and after in vitro stimulation with the model substances E. coli endotoxin, zymosan A, Pam3Cys and Aspergillus versicolor in 25 exposed subjects and 25 control subjects. In vitro stimulation of whole blood with the same components was performed for 20 h and the release of inflammatory mediators IL-8 and IL-1β were quantified. In addition to an enhanced number of blood leucocytes, the expression of the receptors TLR-2, TLR-4 and dectin-1 on blood monocytes was significantly enhanced in exposed subjects. In contrast, no different alteration in expression was detected between exposed and control group after in vitro stimulation with the model substances. The release of IL-8 and IL-1β after stimulation of whole blood with A. versicolor was increased in subjects exposed to moisture damage. Furthermore, in the exposed subjects the IL-1β release was significantly enhanced after in vitro stimulation with E. coli endotoxin (1000 pg/mL). In conclusion, features of the innate immune system (receptor expression and mediator release of monocytes) are altered in subjects exposed to moisture damage which may be a potential explanation for the increased incidence of respiratory health diseases observed in these populations.

Topics: Adult; Aspergillus; Cells, Cultured; Female; Gene Expression Regulation; Humans; Humidity; Interleukin-1beta; Interleukin-8; Lectins, C-Type; Male; Middle Aged; Monocytes; Pilot Projects; Respiratory Tract Diseases; Toll-Like Receptor 2; Toll-Like Receptor 4

Acute respiratory failure in neonates (e.g. ARDS, meconium aspiration pneumonitis, pneumonia) is characterized by an excessive inflammatory response, governing the migration of polymorpho-nuclear leukocytes (PMNLs) into lung tissue and causing consecutive impairment of gas exchange and lung function. Critical to this inflammatory response is the activation of nuclear factor-kappaB (NF-kappaB) that is required for transcription of the genes for many pro-inflammatory mediators. We asked whether the inhibition of NF-kappaB activity using either a selective inhibitor (IKK-NBD peptide) or dexamethasone would be more effective in decreasing NF-kappaB activity and chemokine expression in pulmonary cells. Changes in lung function were repeatedly assessed for 24h following induction of acute respiratory failure and therapeutic intervention. We conducted a randomized, controlled, prospective animal study with mechanically ventilated newborn piglets which underwent repeated airway lavage (20+/-2 [SEM]) to remove surfactant and to induce lung inflammation. Admixed to 100 mg kg(-1) surfactant, piglets then received either IKK-NBD peptide (S+IKK), a selective inhibitor of NF-kappaB activation, its control peptide without intrinsic activity, dexamethasone (S+Dexa), its solvent aqua, or an air bolus only (all groups n=8). After 24h of mechanical ventilation, the following differences were measured: PaO(2)/FiO(2) (S+IKK 230+/-9 mm Hg vs. S+Dexa 188+/-14, p<0.05); ventilation efficiency index (0.18+/-0.01 [3800/(PIP-PEEP)(*)f(*)PaCO(2)] vs. 0.14+/-0.01, p<0.05); extravascular lung water (24+/-1 ml kg(-1) vs. 29+/-2, p<0.05); PMNL in BAL fluid (112+/-21 cells microl(-1) vs. 208+/-34, p<0.05), IL-8 (351+/-117 pg ml(-1) vs. 491+/-144, p=ns) and leukotriene B(4) (23+/-7 pg ml(-1) vs. 71+/-11, p<0.01) in BAL fluid. NF-kappaB activity in the nucleus of pulmonary cells differed by 32+/-5% vs. 55+/-3, p<0.001. Differences between these two intervention groups were more pronounced in the second half of the observation period (hours 12-24). At 24h of mechanical ventilation, inhibition of NF-kappaB activity by IKK-NBD peptide admixed to surfactant as a carrier caused improved gas exchange, lung function and reduced pulmonary inflammation, as evidenced by reduction in PMNL migration into lung tissue due to reduced nuclear NF-kappaB activity. We conclude that IKK-NBD admixture to surfactant in acute neonatal respiratory failure is superior to dexamethasone administration within the fir

Topics: Acute Disease; Animals; Animals, Newborn; Anti-Inflammatory Agents; Blood Cell Count; Bronchoalveolar Lavage Fluid; Dexamethasone; Inflammation; Interleukin-8; Leukotriene B4; Lung Diseases; Neutrophils; NF-kappa B; Organ Size; Pulmonary Gas Exchange; Pulmonary Surfactants; Respiration, Artificial; Respiratory Tract Diseases; Swine

To compare the physiologic and inflammatory response following inhalation of corn dust extract (CDE) and lipopolysaccharide (LPS) solutions in normal subjects.. Randomized, double-blind crossover design.. Fourteen healthy, nonatopic, nonasthmatic, never-smoking volunteers.. On separate visits, subjects underwent a series of four inhalation challenges to LPS or CDE, each containing either a high (6 micrograms/mL) or low (0.9 microgram/mL) endotoxin concentration, and administered at equal Xolumes.. Chest tightness, cough, dyspnea, and sputum production were experienced following both LPS and CDE exposures and with similar frequency at both high and low endotoxin concentrations. LPS and CDE inhalations caused acute declines in FEV1, and the changes in FEV1 from baseline following exposure to both inhalants were not significantly different at both high and low endotoxin concentrations. Following exposure to the high-endotoxin LPS and CDE, no consistent differences in total cell and cytokine (tumor necrosis factor-alpha [TNF-alpha], interleukin-1 beta [IL-1 beta], IL-6, IL-8) concentrations were seen between exposures, although the neutrophil concentration was greater following the LPS exposure (p = 0.01). BAL cellularity and cytokine concentrations following the low-endotoxin LPS and CDE exposure revealed no differences, except for IL-1 beta, which was greater following LPS exposure (p = 0.05). The high-endotoxin LPS and CDE exposures resulted in greater increases in BAL neutrophils and cytokines in comparison to its respective low-endotoxin exposure.. At exposure levels of endotoxin, LPS and CDE result in similar symptoms, changes in airflow, and increases in BAL inflammatory cells and mediators. Moreover, the physiologic and inflammatory response to LPS and CDE appears to be related to the exposure level of endotoxin.

Topics: Adult; Bronchi; Bronchial Provocation Tests; Bronchoalveolar Lavage Fluid; Cross-Over Studies; Double-Blind Method; Dust; Female; Forced Expiratory Volume; Humans; Inflammation; Interleukin-8; Lipopolysaccharides; Male; Middle Aged; Polymerase Chain Reaction; Respiratory Tract Diseases; RNA, Messenger; Tumor Necrosis Factor-alpha; Zea mays

Topics: Aged; APACHE; Cardiovascular Diseases; Cohort Studies; Critical Illness; Disseminated Intravascular Coagulation; Extracellular Traps; Female; Gastrointestinal Diseases; Humans; Intensive Care Units; Interleukin-8; Kidney Diseases; Male; Middle Aged; Mitogen-Activated Protein Kinases; Mortality; Multivariate Analysis; Nervous System Diseases; Neutrophils; Organ Dysfunction Scores; Prospective Studies; Reproducibility of Results; Respiratory Tract Diseases; Risk Assessment; Sepsis; Wounds and Injuries

Indigenous children have much higher rates of ear and lung disease than non-Indigenous children, which may be related to exposure to high levels of geogenic (earth-derived) particulate matter (PM). The aim of this study was to assess the relationship between dust levels and health in Indigenous children in Western Australia (W.A.). Data were from a population-based sample of 1077 Indigenous children living in 66 remote communities of W.A. (>2,000,000 km

Topics: Adolescent; Air Pollutants; Cell Adhesion; Cell Line; Child; Child, Preschool; Ear Diseases; Epithelial Cells; Haemophilus influenzae; Humans; Indigenous Peoples; Infant; Infant, Newborn; Interleukin-8; Odds Ratio; Particulate Matter; Respiratory Tract Diseases; Western Australia

Controversy exists as to the health effects of exposure to asphalt and crumb rubber modified (CRM) asphalt, which contains recycled rubber tyres.. To assess exposures and effects on airway symptoms, lung function and inflammation biomarkers in conventional and CRM asphalt road pavers.. 116 conventional asphalt workers, 51 CRM asphalt workers and 100 controls were investigated. A repeated-measures analysis included 31 workers paving with both types of asphalt. Exposure to dust, nitrosamines, benzothiazole and polycyclic aromatic hydrocarbon (PAH) was measured in worksites. Self-reported symptoms, spirometry test and blood sampling were conducted prework and postwork. Symptoms were further collected during off-season for asphalt paving.. Dust, PAHs and nitrosamine exposure was highly varied, without difference between conventional and CRM asphalt workers. Benzothiazole was higher in CRM asphalt workers (p<0.001). Higher proportions of asphalt workers than controls reported eye symptoms with onset in the current job. Decreased lung function from preworking to postworking was found in CRM asphalt workers and controls. Preworking interleukin-8 was higher in CRM asphalt workers than in the controls, followed by a decrement after 4 days of working. No differences in any studied effects were found between conventional and CRM asphalt paving.. CRM asphalt workers are exposed to higher benzothiazole. Further studies are needed to identify the source of nitrosamines in conventional asphalt. Mild decrease in lung function in CRM asphalt workers and work-related eye symptoms in both asphalt workers were observed. However, our study did not find strong evidence for severe respiratory symptoms and inflammation response among asphalt workers.

Topics: Adult; Air Pollutants, Occupational; Benzothiazoles; Biomarkers; Dust; Eye; Humans; Hydrocarbons; Inflammation; Inhalation Exposure; Interleukin-8; Lung; Male; Middle Aged; Nitrosamines; Occupational Diseases; Occupational Exposure; Occupations; Polycyclic Aromatic Hydrocarbons; Respiratory Tract Diseases; Rubber; Workplace; Young Adult

Neutrophil extracellular traps (NETs) are web-like structures comprising DNA and antimicrobial proteins, expelled from neutrophils during NETosis. Persistence of NETs can be pro-inflammatory, yet their role in respiratory disease remains unclear. This study aimed to investigate the presence of NETs in sputum from patients with asthma and COPD, and the relationship of NETs with inflammatory phenotype and disease severity.. Induced sputum was collected from healthy controls, asthma and COPD patients. Extracellular DNA (eDNA) was quantified by PicoGreen. LL-37, α-defensins1-3, NE, IL-1β and CXCL8 were quantified by ELISA. PAD4 and NLRP3 gene expression was performed using qPCR. NETs were imaged in sputum smears using immunofluorescence microscopy.. Sputum eDNA and NET neutrophil antimicrobial proteins were significantly elevated in asthma and COPD compared with healthy controls. Levels of eDNA and NET components were significantly higher in neutrophilic versus non-neutrophilic asthma and COPD. NETs were clearly visualized in sputum smears. PAD4 mRNA was upregulated in neutrophilic COPD. The level of eDNA was higher in severe asthma. High eDNA levels were associated with heightened innate immune responses, including elevated CXCL8 and IL-1β, and NLRP3 gene expression in both COPD and asthma. Antimicrobial proteins and eDNA were positively correlated with airway neutrophils, and negatively correlated with lung function and symptoms.. NETs are present in the airways of subjects with asthma and COPD. Accumulation of excessive NETs was associated with activation of innate immune responses contributing to disease pathogenesis in chronic airway disease.

Topics: Aged; Chronic Disease; Extracellular Traps; Female; Humans; Immunity, Innate; Inflammation; Interleukin-8; Male; Middle Aged; Neutrophils; Respiratory Tract Diseases; Sputum

The relationship between particulate air pollutants and respiratory symptoms in children has not been consistent among studies, potentially owing to differences in the inflammatory response to different particulate air pollutants. This study aimed to investigate the effect of particulate air pollutants on respiratory symptoms and the inflammatory response in schoolchildren. Three hundred-and-sixty children were included in the study. The children recorded daily respiratory symptom scores for October 2015. In addition, the daily amount of interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-α production was assessed in THP1 cells stimulated with suspended particulate matter (SPM), which was collected every day during the study period. Generalized estimating equation logistic regression analyses were used to estimate the associations among respiratory symptoms and the daily levels of SPM, IL-6, IL-8, and TNF-α. Daily SPM levels were not associated with respiratory symptoms or the daily IL-6, IL-8, and TNF-α levels. Conversely, there was a significant association between respiratory symptoms and the daily IL-6, IL-8, and TNF-α levels. These results suggested that the effects of particulate air pollutants on respiratory symptoms in schoolchildren might depend more on the pro-inflammatory response to them than on their mass concentration.

Topics: Adolescent; Air Pollutants; Child; Female; Humans; Inflammation; Interleukin-6; Interleukin-8; Japan; Male; Particulate Matter; Respiratory Tract Diseases; Time Factors; Tumor Necrosis Factor-alpha

Firefighters exposed to World Trade Center (WTC) dust have developed chronic rhinosinusitis (CRS) and abnormal forced expiratory volume in 1 s (FEV1). Overlapping but distinct immune responses may be responsible for the clinical manifestations of upper and lower airway injury. We investigated whether a panel of inflammatory cytokines, either associated or not associated with WTC-LI, can predict future chronic rhinosinusitis disease and its severity.. Serum obtained within six months of 9/11/2001 from 179 WTC exposed firefighters presenting for subspecialty evaluation prior to 3/2008 was assayed for 39 cytokines. The main outcomes were medically managed CRS (N = 62) and more severe CRS cases requiring sinus surgery (N = 14). We tested biomarker-CRS severity association using ordinal logistic regression analysis.. Increasing serum IL-6, IL-8, GRO and neutrophil concentration reduced the risk of CRS progression. Conversely, increasing TNF-α increased the risk of progression. In a multivariable model adjusted for exposure intensity, increasing IL-6, TNF-α and neutrophil concentration remained significant predictors of progression. Elevated IL-6 levels and neutrophil counts also reduced the risk of abnormal FEV1 but in contrast to CRS, increased TNF-α did not increase the risk of abnormal FEV1.. Our study demonstrates both independent and overlapping biomarker associations with upper and lower respiratory injury, and suggests that the innate immune response may play a protective role against CRS and abnormal lung function in those with WTC exposure.

Topics: Biomarkers; Dust; Firefighters; Forced Expiratory Volume; Humans; Inflammation; Interleukin-6; Interleukin-8; Lung Injury; Male; Neutrophils; New York; Occupational Exposure; Respiratory Tract Diseases; Rhinitis; Risk Assessment; Risk Factors; September 11 Terrorist Attacks; Severity of Illness Index; Sinusitis; Tumor Necrosis Factor-alpha

This study describes a novel nasal lavage method using a pediatric tracheostomy tube and examines intersession repeatability for several clinically and technically relevant parameters. Fourteen healthy subjects were included in this study. Both nasal cavities were washed using a standard amount of saline solution (7 mL) via a pediatric tracheostomy tube, and the 2 samples were pooled for measurement of cytokine concentrations and cell count. Recovery volume was also recorded. For each subject, measurements were repeated on 5 consecutive days. Intersession repeatability of recovery volume, cell count, and cytokine concentrations interleukin (IL)-6 and IL-8 were expressed in terms of mean coefficient of variation, intraclass correlation coefficient, and interitem correlations. Intraclass correlation coefficients and interitem correlation coefficients indicated almost perfect agreement for cell count and IL-8 concentrations. Recovery volume and IL-6 concentrations were more variable. The mean coefficient of variation was low for cell count (2%), IL-8 concentration (3%), and recovery volume (3%), whereas the mean percentage recovery was high (87%). This newly developed nasal lavage technique is repeatable over successive sessions for cytokine concentrations and cell counts in nasal secretions of healthy subjects. This method might be valuable in the study of inflammatory conditions involving the upper respiratory tract.

Topics: Adult; Cell Count; Female; Humans; Interleukin-6; Interleukin-8; Male; Nasal Lavage; Nasal Lavage Fluid; Reproducibility of Results; Respiratory Tract Diseases; Tracheostomy; Translational Research, Biomedical

The goal of this study was to give insight into the lesser known action of neutrophils in the course of bovine respiratory disease (BRD). Neutrophils are principally involved in resistance to infection but under certain conditions these cells participate in lung injury. TNFalpha and IL-8, primary cytokines which play an essential role in neutrophil activation during the inflammatory process, may lead not only to host defence reaction but also to destructive responses. Neutrophil constituents, such as elastase, myeloperoxidase (MPO), alkaline phosphatase (ALKP) and superoxide among others, contribute to tissue destruction. Also, 5-oxo-eicosatetraenoic acid (5-oxo-ETE), the potent activator of neutrophil chemotaxis and degranulation, can cause lung injury. This study revealed that neutrophils under the influence of TNFalpha exacerbated the release of elastase, MPO, ALKP and superoxide. IL-8, in turn, triggered those neutrophils which were isolated from heifers suffering from BRD, and released elastase, ALKP and 5-oxo-ETE, but not MPO or superoxide (O2(-)). The most pronounced degranulative response was observed in the acute form of BRD and a lesser response was seen in the chronic form. The secretory action of neutrophils varied not only depending on the form and phase of the disease but it also diminished successively during recovery.

Topics: Alkaline Phosphatase; Animals; Arachidonic Acids; Cattle; Cattle Diseases; Female; Interleukin-8; Neutrophil Activation; Neutrophils; Pancreatic Elastase; Peroxidase; Respiratory Tract Diseases; Superoxides; Tumor Necrosis Factor-alpha

Chronic obstructive pulmonary disease (COPD) is a disease characterised by inflammation of the peripheral airways involving many inflammatory cells and mediators. IL8 is an important inflammatory mediator that is responsible for the migration and activation of neutrophils. Cellular activity of IL8 is mediated by the receptor CXCR2, and transcription of IL8 is controlled by the cytokine tumour necrosis factor (TNFalpha). The aim of our study was to investigate the influence of single nucleotide polymorphisms in IL8, CXCR2 and TNF-alpha on lung function and respiratory symptoms in subjects from Melbourne, Australia. A total of 1,232 participants completed a detailed respiratory questionnaire, spirometry and measurement of gas transfer. Genotyping for the IL8 -251 T-->A, CXCR2 +785C-->T and TNF-alpha -308G-->A polymorphisms was performed using the tetra-primer ARMS-PCR method. The TNF-alpha A allele was associated with a reduced FEF(25-75) (P = 0.03). Inheritance of the CXCR2 T allele was associated with significantly higher diffusing capacity (P = 0.03) and FEF(25-75) (P = 0.02). No association with the IL8 -251 polymorphism was found. Our results suggest that TNF-alpha is associated with COPD-related phenotypes and the CXCR2 +785 SNP may be important in protecting against pulmonary inflammation. These genes may be important candidates in the modulation of the inflammatory response in the airways.

Topics: Aged; Base Sequence; DNA Primers; Electrophoresis, Agar Gel; Humans; Interleukin-8; Middle Aged; Polymorphism, Genetic; Receptors, Interleukin-8B; Respiratory Tract Diseases; Tumor Necrosis Factor-alpha

It has been shown that exposure in intense exposure in swine barn facilities is associated with increased respiratory symptoms and reduction in pulmonary functions. This study investigated if systemic response could be predicted by FEV(1) response following swine barn exposure.. Naïve males were tested at baseline, low and high endotoxin and dust levels. Subjects were classified as "more responsive" (n = 9) or "less responsive" (n = 11) based on FEV(1) reduction following high endotoxin exposure. Health measures included pulmonary function testing, blood samples and nasal lavage. Environmental samples were collected from the barn.. White blood cells and blood lymphocytes at low exposure were significantly greater in those who were "more responsive" compared to those who were "less responsive". There was a significant increase in blood lymphocytes, serum IL6, total nasal lavage cells and nasal IL8 at high exposure among "more responsive" subjects compared to "less responsive" subjects.. Respiratory response to high-level endotoxin and dust exposure predicts evidence of inflammatory response throughout a range of endotoxin and dust exposures.

Topics: Adolescent; Adult; Air Pollutants, Occupational; Animal Husbandry; Animals; Biomarkers; Cross-Over Studies; Dust; Endotoxins; Housing, Animal; Humans; Hypersensitivity; Interleukin-6; Interleukin-8; Male; Occupational Exposure; Respiratory Function Tests; Respiratory Tract Diseases; Statistics, Nonparametric; Swine

Analysis of the protein components of airway secretions is a potential means of detecting and characterizing biochemical alterations associated with airway diseases.. We evaluated airway protein secretions using the airway epithelial cell line Calu-3 grown at an air-liquid interface. To observe changes in apically secreted proteins, we analyzed the protein content of apical surface fluid (ASF) washings of Calu-3 monolayers treated with ion transport mediators.. Immunoassay screening for antibacterial and inflammatory proteins indicated the presence of measurable levels of lysozyme and IL-8 in Calu-3 ASF. RT-PCR and immunoassay studies indicated that Calu-3 cells do not produce clara cell 10 kDa protein (CC10). The total protein secretion of Calu-3 was not altered by bradykinin, but amiloride and adenosine significantly increased Calu-3 protein secretion. Lysozyme secretion was not altered by bradykinin, but amiloride and adenosine significantly reduced lysozyme secretion. IL-8 secretion was not altered by bradykinin or adenosine, but amiloride significantly decreased IL-8 secretion.. Our results demonstrate the presence of antibacterial protein lysozyme and the pro-inflammatory cytokine IL-8 in Calu-3 ASF and that ion transport mediators such as bradykinin, amiloride and adenosine influence the secretion of Calu-3 ASF proteins.

Topics: Adenosine; Amiloride; Biological Transport, Active; Blotting, Western; Body Fluids; Bradykinin; Diuretics; Epithelial Cells; Humans; Immunoassay; Interleukin-8; Ions; Lactoferrin; Muramidase; Respiratory Tract Diseases; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Vasodilator Agents

In horses prone to developing recurrent airway obstruction (RAO), we tested the hypotheses that the cytokine profile in the bronchoalveolar lavage (BAL) cells of affected horses would reflect a polarized Th-2 response; that cytokine and chemokine alterations would occur within 24 h of allergen exposure; and that allergen exposure would induce alterations in the expression of the transcription factor t-bet (t-box-expressed in T-cells). The expression levels of interleukin-4 (IL-4), IL-13, Interferon-gamma (IFN-gamma), t-bet, IL-8 and granulocyte-macrophage colony stimulating factor (GM-CSF) were measured in BAL cells obtained from control and RAO-susceptible horses during an asymptomatic phase and at 24 h and 5 weeks post-stabling and hay exposure. At each sampling time, BAL neutrophil percentages in the RAO-group exceeded controls. In the RAO-group, only IL-13 expression was decreased 2-fold during the asymptomatic phase. No differences in cytokine or chemokine expression were detected during the acute exposure phase. During the chronic phase, IFN-gamma and IL-8 expression levels were 2.5- and 3-fold greater, respectively, in the RAO-group. No other differences in gene expression were detected. We conclude that the cytokine profile of the airway cells does not reflect a polarized Th-2 response; that increases in IFN-gamma result from a t-bet independent pathway and that chemokines from epithelial or interstitial cells may contribute to early neutrophil influx.

Topics: Allergens; Animals; Bronchoalveolar Lavage Fluid; Cytokines; Female; Horse Diseases; Horses; Interferon-gamma; Interleukin-8; Male; Respiratory Function Tests; Respiratory Tract Diseases; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; T-Box Domain Proteins; Th2 Cells; Transcription Factors

To compare respiratory symptoms and upper airway inflammation in domestic waste collectors and controls, and to find the association between measures of upper airway inflammation on the one hand and exposure concentrations of organic dust or respiratory symptoms on the other hand.. In a cross sectional study among 47 waste collectors and 15 controls, questionnaire data on respiratory symptoms were collected. Nasal lavage (NAL), to assess upper airway inflammation, was performed before and after a work shift at the beginning and at the end of the working week. In NAL fluid, cells were counted and differentiated and concentrations of interleukin 6 (IL6), IL8, tumour necrosis factor-alpha (TNF alpha), and IL1 beta were measured. In collectors, inhalable dust samples were collected in which bacterial endotoxin and mould beta(1-->3)-glucan were assessed.. Prevalence of respiratory symptoms was higher in waste collectors than in controls. Geometric mean exposure concentrations were 0.58 mg/m(3) for dust, 39 EU/m(3) for endotoxin, and 1.3 microg/m(3) for beta(1-->3)-glucan. At the end of the week collectors had higher concentrations of total cells and IL8 in NAL before and after a shift than controls (cells, before 1.9-fold p<0.10, after 3.3-fold p<0.01; IL8, before and after 1.8-fold p<0.05), and after/before work shift ratios of total cells were also higher (2.3-fold p=0.06) in collectors than in controls. Cells in NAL fluid consisted predominantly of neutrophils and epithelial cells, whereas eosinophils and mononuclear cells were rarely found. Exposure to dust and endotoxin was associated with concentrations of IL8 after the shift (p<0.05). Increased concentrations of IL8 (p<0.05) and total cells (p<0.10) after the shift were associated with respiratory symptoms. Concentrations of IL6, TNF alpha, and IL1 beta were not associated with waste collecting, symptoms, or exposure.. Waste collectors show signs of increased upper airway inflammation and respiratory symptoms compared with controls. Exposure to organic dust probably underlies the inflammation mediated by neutrophils that result in respiratory symptoms.

Topics: Adult; Cross-Sectional Studies; Dust; Humans; Interleukin-1; Interleukin-6; Interleukin-8; Male; Nasal Lavage Fluid; Netherlands; Occupational Diseases; Occupational Exposure; Refuse Disposal; Respiration Disorders; Respiratory Tract Diseases; Tumor Necrosis Factor-alpha; Waste Products

Healthy volunteers exposed for 3 hr during weighing of pigs develop an airway inflammation characterized by a massive influx of neutrophilic granulocytes in the upper and lower airways and increased bronchial responsiveness to methacholine. The purpose of the present study was to investigate health effects from exposure during cleaning of the swine confinement building and to evaluate the effect of a respiratory protection device.. Sixteen subjects were exposed for 3 hr during cleaning of a swine confinement room with a high-pressure cleaner. Seven out of sixteen subjects were equipped with a mask during exposure.. The bronchial responsiveness increased in all subjects following exposure, significantly more in the group exposed without a mask (P < 0.05). The cell concentration (mainly neutrophilic granulocytes) in nasal lavage fluid as well as the concentration of interleukin-8, increased significantly only in those subjects exposed without a respiratory protection device. In peripheral blood, an increase of neutrophilic granulocytes was observed in both groups, although it was significantly higher in the group without mask (P < 0.05). The inhalable dust level was 0.94 (0.74 - 1.55) mg/m(3) and respirable dust 0.56 (0.51-0.63) mg/m(3).. Exposure to dust aerosols during the cleaning of the interior of a swine confinement building induces increased bronchial responsiveness and an acute inflammatory reaction in the upper airways. The use of a mask attenuated but did not abolish the inflammatory response. This suggests that gases and/or ultrafine particles in this environment could be important factors in the development of increased bronchial responsiveness.

Topics: Animal Husbandry; Animals; Bronchial Hyperreactivity; Bronchitis; Dust; Humans; Inflammation; Interleukin-8; Leukocyte Count; Methacholine Chloride; Neutrophils; Occupational Diseases; Occupational Exposure; Respiratory Protective Devices; Respiratory Tract Diseases; Swine

The prevalence of respiratory allergies has increased over the last 20 years, highlighting the need for a simple and noninvasive tool to investigate, in a clinical and epidemiological context, airway-inflammation mechanisms encountered in allergic and inflammatory processes. The nose, as the first region of the respiratory tract to come in contact with airborne pollutants, is easily explored with the use of nasal lavage (NL). We evaluated an NL method for adults and children, along with its reproducibility and capacity to separate different subgroups. NL reproducibility, assessed in 10 healthy, nonsmoking adults on three different occasions, was determined with the use of the intraclass coefficient of correlation for such inflammatory markers as total cell count, albumin, urea, neutrophil elastase, alpha(1)-antitrypsin, interleukin-6, and interleukin-8. Using this NL method, we analyzed nasal markers of 50 healthy adults (smokers and nonsmokers) and 12 healthy children. Our NL method demonstrated high reproducibility with regard to total cell count, albumin, urea, and alpha(1)-antitrypsin (intraclass correlation coefficient > 0.75). Compared with NL results in nonsmokers, NL in heavy smokers revealed significant increased concentrations of total cell counts and interleukin-8 and significant decreased concentrations of interleukin-6. These findings suggest that NL can be used as a tool in the assessment of inflammation because it has the correct reproducibility and can discriminate between heavy smokers and nonsmokers. Moreover, the use of this standardized method in children is feasible.

Topics: Adolescent; Adult; Albumins; alpha 1-Antitrypsin; Biomarkers; Cell Count; Child; Enzyme-Linked Immunosorbent Assay; Female; Humans; Hypersensitivity; Inflammation; Interleukin-6; Interleukin-8; Leukocyte Elastase; Male; Middle Aged; Nasal Lavage Fluid; Neutrophils; Reproducibility of Results; Respiratory Tract Diseases; Urea

We determined RANTES (regulated on activation, normal T cell expressed and secreted) and interleukin-8 (IL-8) concentrations, and total white blood cell (WBC) and differential counts in nasal wash samples from rhinovirus-infected infants presenting with wheezing or acute upper respiratory illness alone and compared them with those from healthy infants. RANTES concentrations were significantly greater in acute samples from wheezy patients than in those from patients with acute upper respiratory illness only, or in control samples. IL-8 concentrations and WBC and neutrophil counts were significantly greater in acute samples from wheezy infants and patients with upper respiratory illness alone than in control samples, but they did not differ significantly between the 2 patient groups.

Topics: Chemokine CCL5; Chemokines; Child, Preschool; Humans; Infant; Interleukin-8; Leukocyte Count; Nasal Lavage Fluid; Picornaviridae Infections; Respiratory Sounds; Respiratory Tract Diseases; Rhinovirus

Biomarkers in nasal lavage (NL) fluid may be useful in determining the presence and severity of upper airway inflammation. We studied 18 boilermakers overhauling a large, oil-fired boiler and 11 utility workers who served as controls for 6 wk. NL was performed before (NL1), during (NL2), and after (NL3) the overhaul. We measured nasal fluid levels of interleukins 6 (IL-6) and 8 (IL-8), eosinophilic cationic protein (ECP), and myeloperoxidase (MPO) as markers of response to fuel-oil ash exposure. In boilermakers, MPO was elevated during boiler work versus preboiler work (mean = 33.8 versus 22.7 ng/ml, p < 0.05), and at the 2-wk postexposure lavage (NL3) it had declined to 24.2 ng/ml (p = 0.08). Mean IL-8 levels increased in boilermakers between NL1 and NL2 (mean = 83.8 versus 134.8 pg/ml, p < 0.05), then decreased at NL3 (mean = 134.8 versus 89.0 pg/ml, p < 0.05). Nasal fluid vanadium increased in boilermakers between NL1 and NL2 (median < 1.0 versus 4.7 ppb, respectively, p < 0.05), then decreased at NL3 (median, 4.7 versus < 1.0 ppb, respectively, p < 0. 05). Levels of IL-6 and ECP did not change significantly during the study. Utility workers showed no significant change in any marker during the study period. Particulate matter < 10 micro(m) (PM10) levels were higher for boilermakers than for utility workers before boiler work (geometric mean (GM) = 0.40 versus 0.10 mg/m3, p < 0.05). This difference was more significant during boiler work (GM = 0.47 versus 0.13 mg/m3, p < 0.001). Ozone levels were low during the study. These data suggest that exposure to fuel-oil ash results in acute upper airway inflammation, potentially mediated by increased IL-8 levels and the recruitment and activation of polymorphonuclear leukocytes. These changes were associated with significantly increased PM10 levels and concentrations of upper airway vanadium.

Topics: Adult; Air Pollutants, Occupational; Biomarkers; Blood Proteins; Cytokines; Enzyme-Linked Immunosorbent Assay; Eosinophil Granule Proteins; Fuel Oils; Humans; Inflammation; Inflammation Mediators; Interleukin-6; Interleukin-8; Middle Aged; Nasal Lavage Fluid; Occupational Diseases; Occupational Exposure; Peroxidase; Respiratory Tract Diseases; Ribonucleases; Vanadium Compounds

To characterize the kinetics of grain dust-induced airflow obstruction and inflammation in the lower respiratory tract, we performed serial spirometry and bronchoalveolar lavage (BAL) in human subjects and whole-lung lavage in mice following a single inhalation exposure to comparable dosages of corn dust extract (CDE). Following inhalation of CDE, our human study subjects developed significant airflow obstruction 10 min postexposure which persisted for 48 h. Human subjects and mice had similar acute and persistent changes in lavage cellularity after exposure to CDE. A profound increase in the concentration of lavage neutrophils was present in the initial postexposure lavage in both human subjects and mice. This increase persisted for 96 h in human subjects and 48 h in mice. Small but significant increases in lavage macrophage concentration were present 48 h postexposure in human subjects and at 96 h postexposure in mice. Inhalation of CDE resulted in a significant increase in the concentration of proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in the lavage fluid of both human subjects and mice. Similarly, significant increases in lavage concentrations of IL-8 in humans and macrophage inflammatory protein-2 (MIP-2) in mice occurred after inhalation of CDE. The lavage concentration of all measured proinflammatory cytokines returned to baseline levels by 168 h in humans and 96 h in mice. These findings suggest that a single inhalation challenge of CDE results in airflow obstruction and lower respiratory tract inflammation that may last for several days. These physiologic and inflammatory responses appear to be self-limited with no evidence of persistent injury 1 wk after the inhalation challenge. Moreover, the inflammatory response in the lower respiratory tract after inhalation of grain dust is similar in human subjects and mice, suggesting that the mouse may be an appropriate model for further investigation of grain dust-induced inflammation.

Topics: Adult; Air Pollutants; Animals; Bronchoalveolar Lavage Fluid; Chemokine CXCL2; Dust; Forced Expiratory Volume; Humans; Inflammation; Interleukin-6; Interleukin-8; Leukocyte Count; Male; Mice; Mice, Inbred Strains; Middle Aged; Monokines; Neutrophils; Pulmonary Ventilation; Respiratory Tract Diseases; Spirometry; Tumor Necrosis Factor-alpha; Zea mays

Urinary trypsin inhibitor (UTI), a potential inhibitor for proteinases including neutrophil elastase (NE), trypsin, plasmin, cathepsin B and H has been used for the treatment of lung diseases with the absence of side effects in Japan.. In this study, we investigated the inhibitory effects of UTI on both purified NE and NE activities present in bronchoalveolar fluids from patients with chronic bronchitis. We also investigated the inhibitory capacity of UTI with regard to NE-induced interleukin-8 gene expression in human bronchial epithelial cells by Northern analyses.. UTI inhibited NE activities in bronchoalveolar lavage fluid from patients with chronic bronchitis and of the purified enzyme. In addition, UTI inhibited NE-induced interleukin-8 gene expression and protein secretion in a human bronchial epithelial cell line.. Our results suggest that UTI is applicable to patients with a variety inflammatory lung diseases in which NE plays a pivotal role.

Topics: Bronchi; Cell Line; Epithelium; Gene Expression; Humans; Inflammation; Interleukin-8; Leukocyte Elastase; Neutrophils; Pancreatic Elastase; Respiratory Tract Diseases; RNA, Messenger; Trypsin Inhibitors

To evaluate of the role of interleukin-8 (IL-8), a chemotactic cytokine, in the continuous neutrophil accumulation in the airways of patients with chronic airway disease (CAD) and persistent Pseudomonas aeruginosa infection, we investigated the cell population, IL-8 levels, IL-1 beta levels, tumor necrosis factor (TNF) activities, and neutrophil elastase (NE) activities of bronchoalveolar lavage (BAL) fluids in 17 CAD patients (with P. aeruginosa infections [CAD+PA], n = 9; without any bacterial infections [CAD-PA], n = 8) and 8 normal volunteers. We found significant elevations of neutrophil numbers, IL-8/albumin ratios, and NE/albumin ratios in BAL fluids from CAD patients, in the following rank order: CAD+PA > CAD-PA > normal volunteers. IL-1 beta/albumin ratios were elevated only in CAD+PA, while no TNF bioactivity was detected in BAL fluids. The neutrophil numbers correlated significantly with the IL-8/albumin ratios and NE/albumin ratios in the BAL fluids of CAD patients. When anti-human IL-8 immunoglobulin G was used for neutralizing neutrophil chemotactic factor (NCF) activities in BAL fluids, the mean reduction rate of NCF activities in CAD+PA patients was significantly higher than that in CAD-PA patients. We also evaluated the effects of low-dose, long-term erythromycin therapy in BAL fluids from three CAD+PA and two CAD-PA patients. Treatment with erythromycin caused significant reductions of neutrophil numbers, IL-8/albumin ratios, and NE/albumin ratios in BAL fluids from these patients. To elucidate the mechanism of erythromycin therapy, we also examined whether erythromycin suppressed IL-8 production by human alveolar macrophages and neutrophils in vitro. We demonstrated a moderate inhibitory effect of erythromycin on IL-8 production in Pseudomonas-stimulated neutrophils but not in alveolar macrophages. Our data support the view that persistent P. aeruginosa infection enhances IL-8 production and IL-8-derived NCF activity, causing neutrophil accumulation in the airways and the progressive lung injuries observed in patients with CAD. The clinical efficacy of erythromycin therapy for CAD patients might be partly mediated through a reduced IL-8 production, diminishing neutrophil accumulation and NE release in the airways.

Topics: Adult; Bronchoalveolar Lavage Fluid; Cells, Cultured; Chronic Disease; Erythromycin; Female; Humans; Interleukin-1; Interleukin-8; Leukocyte Elastase; Male; Neutrophils; Pancreatic Elastase; Pseudomonas Infections; Respiratory Tract Diseases; Tumor Necrosis Factor-alpha

We measured NCF activity and examined the characteristics of NCF in bronchoalveolar lavage (BAL) fluid, sputum and culture media of alveolar macrophages. Several kinds of NCF were detected in BAL fluid obtained from normal volunteers, and at least a part of these NCF was thought to be derived from alveolar macrophages. NCF activity, especially complement-derived NCF, was increased in BAL fluid and in sputum obtained from patients with chronic respiratory tract infection. In patients with idiopathic interstitial pneumonia, alveolar macrophage-derived NCF as well as complement derived NCF were increased in BAL fluid. These results indicate that different types of NCF may increase in response to the disease state or pathogenesis, and play important roles in neutrophil accumulation in the respiratory tract.

Topics: Aged; Bronchoalveolar Lavage Fluid; Humans; Interleukin-8; Macrophages; Middle Aged; Pulmonary Alveoli; Respiratory System; Respiratory Tract Diseases