interleukin-8 and Bronchitis

Prostaglandin D(2) (PGD(2)), a major prostanoid produced by activated mast cells, has long been implicated in allergic diseases. Recent studies have shown that PGD(2) exerts its effects through two different G-protein-coupled receptors (GPCRs), the D-prostanoid receptor (DP) and the chemoattractant receptor-homologous molecule expressed on T helper type-2 cells (CRTH2), expressed in various human tissues. The PGD(2)/CRTH2 system mediates the chemotaxis of eosinophils, basophils, and Th2 cells, which are involved in the induction of allergic inflammation. We have reported that normal human bronchial epithelial cells (NHBE) and epithelial cell lines (NCI-H(292)) expressed CRTH2, and PGD(2) induces production of IL-8 and GM-CSF. This review discusses the role of CRTH2/DP on epithelial cells and mentions a possible novel receptor for PGD(2).

Topics: Asthma; Bronchi; Bronchitis; Cell Line; Chemotaxis; Epithelial Cells; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Interleukin-8; MAP Kinase Signaling System; Organ Specificity; Prostaglandin D2; Receptors, Immunologic; Receptors, Prostaglandin; Respiratory Hypersensitivity; RNA, Messenger; Th2 Cells

Morbidity and mortality of chronic obstructive pulmonary disease (COPD) are considerable and still increasing. The disease is gaining increasing socioeconomic importance. The knowledge of underlying mechanisms is of special relevance because of the lack of a curative therapy. Respiratory infections have been identified as the most important triggers of acute exacerbations but recent data suggest that they might also play an important role in COPD pathogenesis. This knowledge might offer new therapeutic perspectives in the future. The aim of this review is, therefore, to describe the inflammatory processes involved and to specify the role of respiratory infections in this context.

Topics: Asthma; Bacterial Infections; Bronchitis; Common Cold; Disease Progression; Humans; Intercellular Adhesion Molecule-1; Interleukin-6; Interleukin-8; Neutrophils; Picornaviridae Infections; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Infections; Rhinovirus; Tumor Necrosis Factor-alpha

Topics: Arthritis, Rheumatoid; Behcet Syndrome; Biomarkers; Bronchitis; Enzyme-Linked Immunosorbent Assay; Humans; Interleukin-10; Interleukin-7; Interleukin-8; Interleukin-9; Lupus Erythematosus, Systemic; Psoriasis; Reagent Kits, Diagnostic; Sjogren's Syndrome

Cystic fibrosis (CF) is the most common genetic autosomal recessive disease in caucasian north-american and european populations. The CF gene codes for a transmembrane glycoprotein called CFTR (Cystic Fibrosis Transmembrane Conductance Regulator), a chloride channel which regulates the luminal secretion of chloride and the active ion and water transport in the airway epithelial cells. Mutations of the CF gene lead to a dysregulation of chloride and sodium channel associated to airway mucus dehydration, neutrophil-dominated airway inflammation and chronic infection responsible for the morbidity and mortality of CF patients. Although a high number of studies has been devoted to the CFTR pleiotropic functions, the chronology of the physiopathological events leading to the airway inflammation linked to mutations of the CF gene is still an open question. The issue of whether airway inflammation takes place before infection or is a consequence of infection during CF pathogenesis is still controversial. It has been recently reported that in broncho-alveolar lavages collected in CF infants, there is an increased level of interleukin IL-8 and abnormal low level of IL-10. The decreased IL-10 production has been confirmed in peripheral blood monocytes as well as in airway cell lines. Under basal conditions, the increased expression of the pro-inflammatory IL-8 cytokine has also been recently observed in the airway liquid secreted by CF naïve humanized airway xenografts and in the supernatant culture of CF human airway epithelial cells. These results suggest that CFTR dysfunction may result in a constitutive pro-inflammatory vs anti-inflammatory imbalance in CF disease. Recent data from the literature suggest that the failure of chloride transport, the maturation defect and mistraffricking of mutated CFTR, lead to its accumulation in the endoplasmic reticulum and activation of NF-kappa B, responsible for the imbalance in the CF airway cell cytokine production.

Topics: Animals; Bacterial Infections; Bronchitis; Bronchoalveolar Lavage Fluid; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Disease Models, Animal; Humans; Interleukin-10; Interleukin-8; Mutation; Virus Diseases

Airway inflammation with eosinophils is now reported to occur not only in asthma but in other airway diseases such as cough variant asthma, chronic cough, atopic cough, episodic symptoms without asthma, allergic rhinitis, and COPD. Although the prevalence of eosinophilic bronchitis (EB) is less than in asthma, the causes, mechanisms and treatment of EB in these conditions appears to be similar to asthma where allergen induced IL-5 secretion and symptoms are readily responsive to inhaled corticosteroids. The prognosis of EB without asthma is not known but it may be a precursor for asthma and, if so, recognition of this syndrome may permit effective treatment and reduction in the rising prevalence of asthma. Induced sputum analysis allows recognition of EB in clinical practice. The place of the asthma treatment paradigm with early and sustained corticosteroid treatment needs to be defined in EB without asthma. Airway wall remodelling can occur in rhinitis, COPD, and cough variant asthma with EB. The mechanisms and long term implications of this complication in EB without asthma need to be clarified.

Topics: Asthma; Bronchitis; Chronic Disease; Cough; Eosinophilia; Humans; Interleukin-5; Interleukin-8; Pulmonary Disease, Chronic Obstructive; Rhinitis, Allergic, Perennial

Cigarette smoking has been implicated in many pulmonary disorders, including chronic bronchitis and chronic obstructive lung disease. Cigarette smoking is associated with increased airway responsiveness. Acute exposure to cigarette smoke increases airway responsiveness in a dose-dependent manner. A superoxide is involved in airway hyper-responsiveness induced by cigarette smoke, perhaps by direct toxic action. Cigarette smokers have increased numbers of neutrophils present in their lower respiratory tract. Acute exposure to cigarette smoke initiates a superoxide-dependent mechanism that, through NF-kappa B activation and IL-8 expression, induces infiltration of neutrophils into the airways in vivo. The alveolar macrophage is one potential source of NF-kappa B activation and IL-8 production after acute exposure to cigarette smoke. Manipulation of NF-kappa B by antioxidants in vivo may be useful in limiting biologic processes such as pro-inflammatory cytokine production, which may lead to neutrophil accumulation in the lung.

Topics: Animals; Antioxidants; Bronchial Hyperreactivity; Bronchitis; Humans; Interleukin-8; Lung Diseases, Obstructive; Macrophages, Alveolar; Neutrophil Infiltration; NF-kappa B; Respiratory System; Smoking; Superoxides

Airway inflammation is a prominent feature of chronic obstructive diseases of the airways, including asthma, bronchiectasis, chronic bronchitis, and diffuse panbronchiolitis. Neutrophils are implicated in the pathogenesis of these diseases. The present review discusses the role of interleukin-8 (IL-8), a neutrophil chemo-attractant, in neutrophil accumulation in the airways, and the mechanisms of inducing IL-8 expression. IL-8 presents in the sputum of patients with inflammatory airway diseases, and accounts in large part for the chemo-attractant activity present. Focusing on Pseudomonas aeruginosa as the stimulus, it was discovered that when a supernatant of bacterial culture is introduced into the airways in vivo, bacterial products induce IL-8 expression in surface airway epithelial cells and the recruitment of neutrophils into the airways. The neutrophil chemotactic activity of the airway fluid was inhibited by an IL-8 antibody. The luminal IL-8 concentration increased in response to instillation of bacteria, and an inhibitor of neutrophil recruitment markedly reduced the IL-8 levels. From these results, it was speculated that bacteria-induced neutrophil accumulation in the airways involves a cascade of events, and that early neutrophil recruitment in response to bacteria is due to epithelium-derived IL-8, while the amplification of the response is due, at least in part, to IL-8 induction in the neutrophils themselves.

Topics: Bronchial Hyperreactivity; Bronchitis; Chemotaxis, Leukocyte; Humans; Interleukin-8; Neutrophils; Tracheitis

This review focuses on bacterial induction and release of inflammatory cytokines and adhesion molecules by human bronchial epithelial cells, with special reference to Haemophilus influenzae, a pathogen commonly associated with chronic bronchitis. Studies investigating the mechanisms underlying bacterial colonization of the airways and bacterial-induced chronic airway inflammation have suggested that these are likely to involve localization of bacteria to the site(s) of infection in the respiratory tract and induction of a local airway inflammation resulting in the initiation of epithelial damage. We have hypothesized that the gross airway epithelial damage observed in chronic infective lung disease is an indirect consequence of proteolytic enzymes and toxic oxygen radicals generated by large numbers of neutrophils infiltrating the airways. Furthermore, the infiltration and activation of the neutrophils is a consequence of increased release of proinflammatory mediators from the host respiratory epithelium, induced by bacterial products, such as endotoxin. This hypothesis is based on studies which have demonstrated that the concentrations of circulating cytokines, such as interleukin (IL)-8 and tumour necrosis factor-alpha (TNF-alpha), which have profound effects on neutrophil activity, are increased in endotoxaemia and that airway epithelial cells are a rich source of these cytokines. Support for this hypothesis is provided by studies of cultured human bronchial epithelial cells incubated either in the absence or presence of purified endotoxin preparations from nontypable and type b H. influenzae strains which have demonstrated that these endotoxins lead to significantly increased expression and/or release of proinflammatory mediators, including IL-6, IL-8, TNF-alpha and intercellular adhesion molecule-1 (ICAM-1). Treatment of the cells with steroids can downregulate the expression and/or release of these inflammatory mediators. Additionally, these studies have demonstrated that culture medium collected from endotoxin-treated cultures, 24 h after treatment, significantly increases neutrophil chemotaxis and adhesion to human endothelial cells in vitro.

Topics: Bacterial Proteins; Bronchi; Bronchitis; Cell Adhesion; Cell Adhesion Molecules; Cells, Cultured; Chemotaxis, Leukocyte; Chronic Disease; Cytokines; Endothelium; Endotoxins; Epithelial Cells; Epithelium; Haemophilus influenzae; Humans; Inflammation Mediators; Intercellular Adhesion Molecule-1; Interleukin-6; Interleukin-8; Neutrophil Activation; Neutrophils; Peptide Hydrolases; Reactive Oxygen Species; Tumor Necrosis Factor-alpha

The events which lead to airway narrowing in bronchial asthma are complex. There is little doubt that mast cell-derived pharmacological agents are involved, at least in part, in the initiation of the asthmatic response. However, the inflammatory response which follows mast cell activation might have more relevance to the daily pattern of asthma than the direct effects of mediators on bronchial tissue. Although the IgE mediated release of mediators from sensitized mast cells seems to play a role in pathogenesis in some individuals for some of the time, there is now increasing awareness that mast cells are also triggered by a number of non-immunological stimuli such as exercise/cold air, infection and agents which activate the complement system. Mast cell mediators are either pre-formed within granules or generated from membrane-bound phospholipids. The pre-formed mediators include histamine, various chemotactic peptides including ECF-A and the high molecular weight neutrophil chemotactic factor (NCF), proteases, glycosidases, and the heparin proteoglycan. The membrane-derived agents include the lipoxygenase products (e.g. LTB4 and the "SRS-A" leukotrienes-LTC4/D4/E4), prostaglandins and thromboxane in addition to the PAF-ace-tether (AGEPC). The mediators are diverse both in chemical composition and modes of actions. However, many of the pathological features of bronchial asthma can be explained on the basis of their recognised actions. These can be summarised as follows. Bronchial smooth muscle constriction (histamine, LTC4, LTD4, LTE4, PGF2 alfa, PGD2 and PAF); mucosal oedema (increased permeability--histamine, LTC4, LTD4 and PAF; vasodilation--PGD2, PGE2); mucous plugging (histamine, mono-HETEs and LTC4); inflammatory cell infiltrate (NCF, ECF-A peptides, HETEs, LTB4 and PAF); desquamation of epithelium (proteases, glycosidases, together with lysosomal enzymes, and basic proteins derived from neutrophils and eosinophils). It is likely that mild, easily reversible, episodic asthma is due largely to bronchial smooth muscle contraction whereas the late sustained response is more indicative of an inflammatory response, and dependent on the infiltration of neutrophils and eosinophils as the result of mediators which recruit and activate leucocytes. Much of the evidence for this is based on the demonstration that NCF concentrations in the serum are elevated during early and late phase, antigen- and exercise-induced asthma. Moderate to severe asthma is likely t

Topics: Animals; Arachidonic Acid; Arachidonic Acids; Asthma; Asthma, Exercise-Induced; Bronchitis; Chemotactic Factors; Humans; Hypersensitivity; Immunoglobulin E; Interleukin-8; Mast Cells; Platelet Activating Factor; SRS-A

Post-operative pulmonary complications such as systemic inflammatory response syndrome (SIRS), acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are strongly associated with morbidity and mortality after esophagectomy. Post-operative administration of sivelestat sodium hydrate (sivelestat), a selective inhibitor of neutrophil elastase (NE), has been shown to improve the post-operative clinical course after esophagectomy. This study aimed to evaluate the effect of prophylactic administration of sivelestat on bronchial inflammatory responses. We randomized 24 patients into two groups. One group received 0.2 mg/kg/h sivelestat from the induction of anesthesia to post-operative day 1 (sivelestat group) and the other group received the same amount of physiological saline (control group). Bronchial alveolar epithelial lining fluid (ELF) samples were obtained from both groups at the induction of anesthesia and at the end of surgery. The serum and ELF levels of interleukin (IL)-6 and IL-8 were measured by enzyme-linked immunosorbent assay, and NE activity was spectrophotometrically determined using the same samples. Although IL-6 levels in the ELF significantly increased at the end of surgery compared with the pre-operative levels in both groups, the IL-8 levels and NE activity did not significantly increase at the end of the surgery compared to the corresponding pre-operative values in the sivelestat group. Moreover, IL-8 levels and NE activity in the ELF were significantly reduced at the end of surgery in the sivelestat group compared with corresponding values in the control group. The durations of ALI and ARDS were apparently shorter in the sivelestat group and the duration of SIRS was significantly shorter in the sivelestat group compared to the control group. We demonstrated that prophylactic use of sivelestat mitigated bronchial inflammation by suppressing NE activity and IL-8 levels in the ELF and shortened the duration of SIRS after transthoracic esophagectomy.

Topics: Acute Lung Injury; Aged; Bronchitis; Esophagectomy; Female; Glycine; Humans; Interleukin-6; Interleukin-8; Leukocyte Elastase; Male; Middle Aged; Postoperative Complications; Premedication; Respiratory Distress Syndrome; Respiratory Function Tests; Serine Proteinase Inhibitors; Sulfonamides; Systemic Inflammatory Response Syndrome; Treatment Outcome

Obstructive sleep apnea syndrome (OSA) is associated with systemic and upper airway inflammation. Pharyngeal inflammation has a potential role in upper airway collapse, whereas systemic inflammation relates to cardiovascular morbidity. However, the presence of an inflammatory involvement of lower airway has been poorly investigated.. The aim of the study was to demonstrate an inflammatory process at the bronchial level in patients with OSA and to analyze effects of continuous positive airway pressure (CPAP) application and humidification on bronchial mucosa.. The study was conducted by using sequential induced sputum for cell analysis and IL-8 production, nitric oxide exhalation measurement, and methacholine challenge before and after CPAP.. Bronchial neutrophilia and a high IL-8 concentration were observed in untreated OSA compared with controls (75% +/- 20% vs 43% +/- 12%, P < .05; and 25.02 +/- 9.43 ng/mL vs 8.6 +/- 3.7 ng/mL, P < .001, respectively). IL-8 in sputum supernatant was correlated to apnea hypopnea index (P < .01; r = 0.81). After 1 month of CPAP, this inflammatory pattern remained unchanged, and an increase in airway hyperresponsiveness (AHR) was observed (P < .001).. Obstructive sleep apnea syndrome is associated with bronchial inflammation. Our data demonstrate CPAP effect on the development of AHR, possibly facilitated by the pre-existing inflammation. Both issues should be evaluated during long-term CPAP use.. Results showing a spontaneous bronchial inflammation in OSA and the development of a CPAP-related AHR require a long-term follow-up to evaluate consequences on chronic bronchial obstruction.

Topics: Adult; Bronchi; Bronchial Hyperreactivity; Bronchitis; Bronchoconstrictor Agents; Continuous Positive Airway Pressure; Exhalation; Female; Humans; Interleukin-8; Male; Methacholine Chloride; Middle Aged; Neutrophils; Nitric Oxide; Respiratory Mucosa; Sleep Apnea, Obstructive; Sputum

Chronic obstructive pulmonary disease (COPD) is accompanied by both airway and systemic inflammation and by oxidative stress. This study aimed to characterise the relationship between oxidative stress and inflammatory components in induced sputum and blood.. We studied blood and sputum samples from stable COPD patients (mean FEV1 60.5+/-7.5% predicted) at baseline (no treatment) and after 10 weeks treatment with either inhaled steroid, fluticasone propionate (FP) (1000 microg/d) or 10 weeks treatment with N-acetylcysteine (600mg/d) (NAC). We assessed the inflammatory markers (IL-8, ECP, sICAM-1, NE) in sputum and serum and we compared them with blood markers of oxidative stress (SOD, GPx, TEAC, albumin, vitamin E and A).. At baseline blood sICAM-1 correlated with IL-8 levels (P<0.01, r = 0.62) and negatively with GPx (P<0.01, r = -0.63) and with TEAC (P<0.05, r = -0.53). TEAC correlated positively with GPx (P<0.01, r = 0.70). Correlation between sICAM and IL-8 disappeared after NAC treatment. The correlation between sICAM and GPx disappeared after FP treatment. The correlation between TEAC and GPx was maintained after both NAC and FP.. The relationship between markers of inflammation, adhesion and antioxidant capacity is significantly modulated by treatment with N-acetylcysteine or inhaled corticosteroids.

Topics: Administration, Inhalation; Aged; Androstadienes; Anti-Inflammatory Agents; Antioxidants; Biomarkers; Bronchitis; Cross-Over Studies; Female; Fluticasone; Forced Expiratory Volume; Humans; Interleukin-8; Male; Middle Aged; Oxidative Stress; Pulmonary Disease, Chronic Obstructive; Spirometry; Sputum; Vital Capacity

Bacterial endotoxin (lipopolysaccharides (LPS)) is normally present in the wall of Gram-negative bacteria and has potent pro-inflammatory properties. Exposure to LPS has been shown to induce neutrophilic airway inflammation in humans. The aim of this investigation was to study the early inflammatory responses to LPS exposure in human airway mucosa in vivo. In total, 15 healthy nonsmoking volunteers participated. Bronchoscopy was performed on two separate occasions, 3 h after saline inhalation and after inhalation of 50 mug LPS in saline. Endobronchial mucosal biopsy specimens were taken and stained immunohistochemically using a panel of monoclonal antibodies directed against mitogen-activated protein kinases (MAPKs), transcription factors, cytokines, adhesion molecules and inflammatory cells. Expression of p38 MAPK increased as a consequence of LPS exposure, as determined by both total epithelial staining and nuclear location. These two responses were strongly associated. Epithelial expression of interleukin-8 showed a tendency towards a significant increase after LPS compared to saline. Epithelial mast cell numbers were increased after LPS, whereas neutrophil numbers were unchanged. Inhalation of lipopolysaccharide induced activation of the bronchial epithelium, as demonstrated 3 h after exposure by increased expression of p38 mitogen-activated protein kinase and interleukin-8, and may represent early regulatory steps in the subsequent development of a neutrophilic bronchial inflammation.

Topics: Adult; Bronchitis; Cytokines; Female; Humans; Interleukin-8; Lipopolysaccharides; Male; p38 Mitogen-Activated Protein Kinases; Respiratory Mucosa; Transcription Factors

alpha1-Antitrypsin (AAT) deficiency predisposes to bronchitis and emphysema associated with neutrophilic airway inflammation. The efficacy of augmentation therapy has not been proven clinically or by demonstrating an effect on airway inflammation. We treated 12 patients with four infusions of Prolastin (60 mg/kg) at weekly intervals and monitored both the serum and secretion concentrations of AAT as well as markers of neutrophilic inflammation, including myeloperoxidase, elastase, and the neutrophil chemoattractants interleukin-8 and leukotriene B(4). Serum AAT rose and was maintained above the protective threshold. In addition, AAT concentrations in the sputum rose from a mean of 0.17 microM (SEM +/- 0.04) before therapy to concentrations similar to nondeficient subjects (0.43 +/- 0.12) 1 week after the first infusion (p < 0.01). This was associated with a reduction in elastase activity (p < 0.002) and the chemoattractant leukotriene B(4) (p < 0.02), which fell from a median baseline value of 13.46 nM (range, 4.17-55.00) to 8.62 nM (4.23-21.59) the day following the last infusion. Although median values for myeloperoxidase and interleukin-8 also fell, the changes failed to achieve statistical significance. In summary, short-term therapy with AAT increased lung secretion concentrations and was associated with a fall in leukotriene B(4), which is thought to be central to the airway inflammation of AAT deficiency.

Topics: alpha 1-Antitrypsin; alpha 1-Antitrypsin Deficiency; Biomarkers; Bronchitis; Dose-Response Relationship, Drug; Drug Administration Schedule; Enzyme-Linked Immunosorbent Assay; Female; Humans; Infusions, Intravenous; Interleukin-8; Leukotriene B4; Male; Pancreatic Elastase; Peroxidase; Prognosis; Reference Values; Sensitivity and Specificity; Sputum; Treatment Outcome

Viable bacteria are often isolated from airway secretions in clinically stable patients with chronic bronchitis. We hypothesized that the number of organisms and bacterial species might be important modulators of airway inflammation.. We performed quantitative sputum cultures in 160 stable patients [55 with chronic obstructive pulmonary disease (COPD) and normal serum alpha(1)-antitrypsin levels, 62 with COPD and severe alpha(1)-antitrypsin deficiency (PiZ), and 43 with idiopathic bronchiectasis]. The results were related to several indicators of the mechanisms and severity of airway inflammation.. Airway bacterial load correlated with sputum myeloperoxidase level, an indirect measure of neutrophil activation and number (r = 0.50, P<0. 001); sputum neutrophil chemoattractants [interleukin-8 level (r = 0. 68, P<0.001) and leukotriene B4 level (r = 0.53, P<0.001)]; sputum leukocyte elastase activity (r = 0.55, P<0.001); and albumin leakage from serum to sputum (r = 0.26, P<0.01). Markers of inflammation increased at bacterial loads of 10(6) to 10(7) colony-forming units per milliliter, and increased progressively with increasing bacterial load. For example, the median (interquartile range) sputum myeloperoxidase level was 0.3 U/mL (0.1 to 0.5 U/mL) for patients who were not colonized or who had mixed normal oropharyngeal flora alone; 0.5 U/mL (0.2 to 0.7 U/mL) for patients with 10(5) to 10(6) colony-forming units per milliliter (P = 0.07); 0.5 U/mL (0.3 to 1.2 U/mL) for patients with 10(6) to 10(7) colony-forming units per milliliter (P<0.01); 0.7 U/mL (0.3 to 1.2 U/mL) for patients with 10(7) to 10(8) colony-forming units per milliliter (P <0.005); and 2.4 U/mL (0.7 to 4.8 U/mL) for patients with 10(8) or greater colony-forming units per milliliter (P<0.0001). The bacterial species influenced airway inflammation; for example, sputum myeloperoxidase activity was greater (P<0.005) in patients colonized with Pseudomonas aeruginosa [median 32 U/mL (interquartile range, 20 to 65 U/mL)] than those colonized with nontypeable Hemophilus influenzae [4 U/mL (2 to 31 U/mL)], which in turn was greater (P = 0.01) than among those colonized with Moraxella catarrhalis [1.1 U/mL (0.6 to 1.8 U/mL)]. We did not find a relation between bacterial load and lung function.. The bacterial load and species contribute to airway inflammation in patients with stable chronic bronchitis. Further studies are required to determine the consequences of bacterial colonization on patient morbidity and decline in lung function.

Topics: Aged; Bacteria; Biomarkers; Bronchitis; Bronchoalveolar Lavage Fluid; Chi-Square Distribution; Chronic Disease; Colony Count, Microbial; Female; Humans; Inflammation Mediators; Interleukin-8; Leukotriene B4; Lung Diseases, Obstructive; Male; Middle Aged; Peroxidase; Prognosis; Reference Values; Severity of Illness Index; Sputum; Statistics, Nonparametric; Stem Cells

The aim of this study was evaluation of interleukin-6 (IL-6) and interleukin-8 (IL-8) in creation of inflammation of lower airways in patients with chronic bronchitis. 32 patients with chronic bronchitis and 14 subjects of control group took part in this study. Spirometry (Jaeger eq.), bronchofibroscopy and bronchoalveolar lavage (Olympus eq.) were performed in every patient. Cytology and concentration of IL-6 and IL-8 (kits from R&D) were measured in 1 ml of lavage fluid recovered. The increased levels of IL-6 and IL-8 in BAL were correlated with clinical parameters. We conclude that these two cytokines participate in creation of inflammatory changes of lower respiratory tract in chronic bronchitis.

Topics: Adult; Biomarkers; Bronchitis; Bronchoalveolar Lavage Fluid; Chronic Disease; Female; Humans; Inflammation; Interleukin-6; Interleukin-8; Male; Middle Aged

The aim: To examine the composition of the oral microbiome in young children with laryngopharyngeal reflux (LPR) and its role the development of recurrent respiratory diseases.. Materials and methods: There were examined 38 children with physiological gastroesophageal reflux (GER), 18 children with LPR who had a medical history of recurrent bronchitis and 17 healthy children (control group). The study included the collection of anamnesis, objective examination. The qualitative and quantitative microbial composition of the upper respiratory tract was performed obtained by oropharyngeal deep swab. Salivary pepsin level and IL-8 were determined by enzyme-linked immunosorbent assay.. Results: This research showed significant alterations in the oral microbiome of patients with GER and LPR as compared to healthy control. We found that gram-negative microbiota such as Klebsiella pneumoniae, Escherichia coli, Proteus vulgaris, Proteus spp. and Candida albicans were identified in children with GER and LPR compared to the healthy control. At the same time, the amount of such a representative of the normal microbiome as Streptococcus viridans in children with LPR was sharply reduced. There were established a much higher mean salivary pepsin level of the patients with LPR than in the GER and control group. We found the association between high pepsin levels, saliva IL-8 levels and frequency of respiratory pathology in children with LPR.. Conclusions: Our study confirms that increased levels of pepsin in saliva are a risk factor for recurrent respiratory diseases in children with LPR.

Topics: Bronchitis; Child; Child, Preschool; Gastroesophageal Reflux; Gastrointestinal Microbiome; Humans; Interleukin-8; Laryngopharyngeal Reflux; Mouth; Pepsin A; Recurrence; Risk Factors; Saliva

Inflammatory processes, including respiratory symptoms, can be induced among workers in composting plants exposed to bioaerosols containing microorganisms and their compounds. We evaluated inflammatory processes in the lower respiratory tract via cellular and soluble mediator profiles in induced sputum (IS). IS samples of 140 current (35% smokers) and 49 former compost workers (29% smokers) as well as 29 white-collar workers (17% smokers) were collected and analyzed for the cell count and composition, and for soluble biomarkers. Significant differences between current and former compost workers and white-collar workers were detected for total cell count (p=0.0004), neutrophils (p=0.0045), sCD14 (p=0.008), and 8-isoprostane (p<0.0001). IS of non-smoking former compost workers showed lower concentrations of IL-8, total protein, immunoreactive MMP-9 and sCD14, compared with non-smoking current compost workers. 10.1% of the study population was suffering from chronic bronchitis with significant differences (p=0.018) between former compost workers (24.5%), current workers (5%), and white-collar workers (10.3%). Significantly lower IL-8 (p=0.0002), neutrophils (p=0.001), and MMP-9 (p=0.0023) values were measured in healthy subjects compared with subjects with chronic bronchitis. In conclusion, changes in lower airways were detected by analysis of biomarkers in IS of current exposed and, to a lesser extent, in IS of former compost workers. These effects are especially pronounced in subjects with chronic bronchitis.

Topics: Adult; Air Pollutants, Occupational; Biomarkers; Blood Proteins; Bronchitis; Cell Count; Chronic Disease; Cross-Sectional Studies; Dinoprost; Female; Humans; Interleukin-8; Lipopolysaccharide Receptors; Male; Matrix Metalloproteinase 9; Middle Aged; Neutrophils; Occupational Exposure; Pneumonia; Smoking; Soil; Sputum

When exacerbation of chronic obstructive pulmonary disease (AECOPD) occurs frequently, patients have high levels of airway and systemic inflammation and a poor quality of life. This study compared the nature and course of systemic and airway inflammation during AECOPD between patients who experienced frequent exacerbations and those with non-frequent exacerbations.. Consecutive hospitalized patients with AECOPD were recruited and divided into 2 groups according to the frequency of AECOPD they had experienced in the previous year. Frequent exacerbators (defined as 2 or more AECOPD in the previous year) and non-frequent exacerbators (defined as zero or 1 AECOPD in the previous year). Inflammatory (interleukin 6, interleukin 8, myeloperoxidase, and C-reactive protein) and clinical (dyspnea, COPD assessment test (CAT), and peak expiratory flow) indices were assessed on the day of admission before starting therapy, day 7 of treatment, the day of planned discharge (day 10-14), and 8 weeks after discharge.. We analyzed data from 135 patients; 78 (57.8%) were non-frequent exacerbators and 57 (42.2%) were frequent exacerbators. In both groups, the inflammatory and clinical indices at day 7, the day of planned discharge (day 10-14), and 8 weeks were significantly improved compared to those at admission. Frequent exacerbators had a smaller reduction in their inflammatory indices and CAT scores between exacerbation onset and all the other time points compared with infrequent exacerbators.. Frequent exacerbators have a reduced response to treatment of AECOPD in terms of inflammatory indices and quality of life.

Topics: Aged; Bronchitis; C-Reactive Protein; China; Dyspnea; Female; Humans; Inflammation; Interleukin-6; Interleukin-8; Lung Diseases, Obstructive; Male; Middle Aged; Peak Expiratory Flow Rate; Peroxidase; Prospective Studies; Quality of Life; Recurrence; Statistics, Nonparametric; Time Factors

IL-8 is an important activator and chemoattractant for neutrophils that is produced by normal human bronchial epithelial (NHBE) cells through mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) p65 pathways. Dapsone, a synthetic sulfone, is widely used to treat chronic neutrophil dermatoses. We investigated the effects of dapsone on polarized IL-8 secretion from lipopolysaccharide (LPS)-stimulated NHBE cells and further evaluated its ability to decrease LPS-induced inflammation in the ferret airway.. NHBE cells were grown at air-liquid interface (ALI) to ciliated differentiation. Baseline and endotoxin (LPS)-stimulated IL-8 secretion was measured by enzyme-linked immunosorbent assay at air and basal sides with and without dapsone. Western blotting was used to determine signaling pathways. In vivo, ferrets were exposed to intratracheal LPS over a period of 5 days. Once inflammation was established, oral or nebulized dapsone was administered for 5 days. Intraepithelial neutrophil accumulation was analyzed histologically, and mucociliary transport was measured on the excised trachea.. Dapsone, 1 μg/mL, did not influence unstimulated (basal) IL-8 secretion. Apical LPS stimulation induced both apical and basolateral IL-8, but basolateral LPS increased only basolateral IL-8. Dapsone inhibited polarized IL-8 secretion from ALI-conditioned cells. Dapsone also decreased LPS-induced IL-8 mRNA level. LPS led to phosphorylation of extracellular signal-regulated kinase 1/2, but not p38 MAPK or c-Jun NH(2)-terminal kinase. LPS also induced NF-κB p65 phosphorylation, an effect that was inhibited by dapsone. Both oral and aerosol dapsone decreased LPS-induced intraepithelial neutrophil accumulation, but only treatment with aerosol dapsone restored mucociliary transport to normal.. Dapsone, given either systemically or as an aerosol, may be useful in treating neutrophilic airway inflammation.

Topics: Administration, Oral; Aerosols; Animals; Anti-Inflammatory Agents; Bronchi; Bronchitis; Cell Survival; Cells, Cultured; Dapsone; Disease Models, Animal; Epithelial Cells; Ferrets; Humans; Interleukin-8; Lipopolysaccharides; Male; Mitogen-Activated Protein Kinase Kinases; Neutrophils; Phosphorylation; Transcription Factor RelA; Treatment Outcome

To describe the clinical manifestations of parainfluenza virus (PIV) infection and to characterize biochemical markers of PIV disease severity.. We reviewed the medical records of 165 children who had a nasal wash culture positive for PIV at our institution between 1998 and 2008. Nasal wash samples were assayed for 26 inflammatory mediators using Luminex bead proteomics.. A total of 153 patients, ages 2 weeks to 12 years, with single virus infection were included in our final analysis. Fifty-two patients were infected with PIV1, 19 with PIV2, 74 with PIV3, and 8 with PIV4. Lower respiratory tract infection (LRTI) was diagnosed in 67 (44%) patients, 21 (14%) had laryngotracheobronchitis, and 49 (32%) had an upper respiratory infection other than laryngotracheobronchitis. LRTI was diagnosed in 54% of patients infected with PIV3, 35% of those infected with PIV1, 26% of those with PIV2, and 50% of those with PIV4. Compared with uninfected control patients, PIV-infected patients had higher nasal wash concentrations of interleukin-6, CX-chemokine ligand 8 (CXCL8 or interleukin-8), CCL3 (macrophage inflammatory protein-1alpha), CCL4 (macrophage inflammatory protein-1beta), CXCL9 (monokine induced by interferon gamma), and CCL5 (regulated upon activation, normal T cell expressed and secreted (RANTES). Patients with LRTI, moderate or severe illness, and PIV 1 or 3 (respirovirus) infection had higher nasal wash concentrations of CXCL8 when compared with patients with upper respiratory infection, mild illness, or PIV 2 and 4 (rubulavirus) infection (P < 0.05).. PIV infection causes a spectrum of illnesses associated with the expression and release of several proinflammatory mediators. Of note, elevated concentrations of CXCL8 in nasal wash samples are associated with more severe forms of PIV disease.

Topics: Bronchitis; Child; Child, Preschool; Humans; Infant; Infant, Newborn; Inflammation Mediators; Interleukin-8; Laryngitis; Nasal Lavage Fluid; Parainfluenza Virus 1, Human; Parainfluenza Virus 2, Human; Parainfluenza Virus 3, Human; Parainfluenza Virus 4, Human; Paramyxoviridae Infections; Respiratory Tract Infections; Severity of Illness Index; Tracheitis

Chronic obstructive pulmonary disease (COPD) has a genetic component, explaining susceptibility. Tumor necrosis factor (TNF)-alpha polymorphisms have been associated with COPD, but it is unclear if genotype influences clinical phenotype, protein expression, and bioactivity.. To determine if a functional polymorphism was important by assessing TNF-alpha expression and activity and its association with clinical severity over time.. Patients with COPD with rs361525 polymorphism were matched to patients with COPD without rs361525 polymorphism. TNF-alpha, its antagonists, and downstream mediators were measured in plasma and sputum. To determine TNF-alpha bioactivity, IL-8 secretion from primary bronchial epithelial cells (PBECs) was measured, and neutrophil migration was assessed using sputum from both subject groups in the presence and absence of TNF-alpha antibody. Subjects were followed annually and compared.. Patients with polymorphism had more chronic bronchitis, a lower body mass index, and a greater annual decline in FEV(1) than patients with COPD without rs361525 polymorphism. TNF-alpha concentrations were 100-fold higher in airway secretions from the patients with the rs361525 polymorphism, with no difference in TNF-alpha antagonists. Their lung secretions contained more IL-8 and myeloperoxidase, consistent with downstream inflammation. Sputum from patients with rs361525 polymorphism induced greater secretion of IL-8 from PBECs and increased neutrophil migration. These effects could be abrogated by TNF-alpha antibody, demonstrating the bioactivity of TNF-alpha in lung secretions from this group.. This TNF-alpha polymorphism is associated with clinical features of disease including progression. There is clear evidence of TNF-alpha overexpression and bioactivity with neutrophilic inflammation. The polymorphism is likely to be a factor that influences a COPD disease phenotype and its progression.

Topics: Adult; Aged; Body Mass Index; Bronchi; Bronchitis; Case-Control Studies; Cell Movement; Disease Progression; Epithelial Cells; Female; Forced Expiratory Volume; Genotype; Humans; Interleukin-8; Male; Middle Aged; Neutrophils; Peroxidase; Phenotype; Polymorphism, Genetic; Pulmonary Disease, Chronic Obstructive; Severity of Illness Index; Sputum; Tumor Necrosis Factor-alpha

Cigarette smoking causes inflammatory responses in the airways. However, not all smokers exhibit the development of airflow limitation. This study was designed to determine the implications of small airways inflammation in the development of airflow limitation in smokers by our newly explored method. Twenty-eight smokers (15 smokers without airflow limitation and 13 with airflow limitation) were included in this study. Levels of interleukin-8 (IL-8) and 8-isoprostane were measured in epithelial lining fluid (ELF) from central and peripheral airways separately collected using a bronchoscopic microsampling technique. 8-isoprostane levels in ELF from central or peripheral airways did not significantly differ between the two groups. However, these levels were markedly higher in peripheral than in central airways. Similarly, IL-8 levels in ELF from central airways did not significantly differ between the two groups. In smokers without airflow limitation, IL-8 levels were not higher in peripheral than in central airways. In contrast, in smokers with airflow limitation, IL-8 levels were significantly higher in peripheral airways. Moreover, in smokers with airflow limitation, 8-isoprostane levels in central or peripheral airways were not significantly correlated with FEV(1). However, IL-8 levels in peripheral airways were inversely correlated with FEV(1), though those levels in central airways were not. Thus our technique provides a novel method for ELF sampling from central or peripheral airways separately, and the preliminary evidence that support differences in oxidative stress and neutrophil chemotactic stimulus in these two locations.

Topics: Aged; Biomarkers; Bronchi; Bronchioles; Bronchiolitis; Bronchitis; Bronchoscopy; Dinoprost; Extracellular Fluid; Female; Humans; Interleukin-8; Male; Middle Aged; Prospective Studies; Respiratory Mucosa; Smoking; Statistics, Nonparametric

Alcoholics are known to have more severe airway diseases of the lung, such as bronchitis. Little is known about why this phenomenon is observed. We hypothesized that alcohol may modulate Toll-like receptor 2 (TLR2), which regulates inflammation caused by gram-positive bacteria.. Airway epithelial cells [primary bronchial epithelial cells (NHBE) and 16HBE 14o-] were exposed to 0 to 100 mM alcohol for 0 to 24 hours. Real time PCR was used to quantify TLR2 mRNA. Protein levels of TLR2 were determined using Western blots and fluorescence activated cell sorting (FACS) on cells exposed to 0, 50, and 100 mM alcohol. Finally, cells were "primed" with alcohol, stimulated with a TLR2 agonist (peptidoglycan), and interleukin 8 (IL-8) release was measured.. Alcohol, at biologically relevant concentrations (25 to 100 mM), caused a 2 to 3-fold time- and concentration-dependent increase in TLR2 mRNA in normal human bronchial epithelial cells and 16HBE 14o- cells. Western blots for TLR2 revealed a qualitative increase in TLR2 protein in cells exposed to 100 mM alcohol. FACS showed that TLR2 was quantitatively increased on the surface of airway epithelial cells that were exposed to alcohol. Airway cells that were primed with alcohol produced nearly twice as much IL-8 in response to 40 ng of peptidoglycan than naive cells.. Alcohol upregulates TLR2 message and protein in the airway epithelium. This leads to exaggerated inflammation in response to environmental stimuli that would normally be well tolerated in airway epithelial cells. This may be a partial explanation of why alcoholics have more severe airway disease than nonalcoholics.

Topics: Alcoholism; Bronchi; Bronchitis; Cells, Cultured; Central Nervous System Depressants; Dose-Response Relationship, Drug; Epithelial Cells; Ethanol; Humans; Interleukin-8; Peptidoglycan; RNA, Messenger; Time Factors; Toll-Like Receptor 2; Up-Regulation

To evaluate the relationship between pro-inflammatory and pro-remodeling mediators and severity and control of asthma in children, the levels of IL-8, MMP-9, TIMP-1 in induced sputum supernatants, the number of sputum eosinophils, as well as FeNO, were investigated in 35 asthmatic children, 12 with intermittent (IA) and 23 with moderate asthma (MA), and 9 controls (C). The patients with asthma were followed for 1 yr and sputum was obtained twice during the follow-up. Biomarker levels were correlated with the number of exacerbations. We found that IL-8, MMP-9, TIMP-1 and the numbers of eosinophils in induced sputum, as well as FeNO, were increased in children with IA and MA in comparison to C. The ongoing inflammation was confirmed by increased nuclear p65 NF-kappaB subunit localization in sputum cells. In MA, FeNO measurements, sputum eosinophils and IL-8 levels, positively correlated with the occurrence of disease exacerbations during a 1-yr follow-up. According to FeNO, sputum eosinophils and IL-8 sputum concentrations, and the number of exacerbations, two distinct phenotypes of MA were identified. This study shows that the presence of bronchial inflammation is detectable in the airways of some IA, as well as in the airways of MA, despite the regular ICS treatment. This study also proposes the need to perform large prospective studies to confirm the importance of measuring specific biomarkers in induced sputum, concomitantly to FeNO analyses, to assess sub-clinical airway inflammation and disease control in children with asthma.

Topics: Adolescent; Asthma; Biomarkers; Bronchitis; Child; Disease Progression; Eosinophils; Female; Follow-Up Studies; Humans; Interleukin-8; Leukocyte Count; Male; Matrix Metalloproteinase 9; Sputum; Tissue Inhibitor of Metalloproteinase-1

Protracted bacterial bronchitis (PBB) is a common cause of paediatric chronic moist cough. PBB is defined as the presence of isolated chronic moist cough which resolves with antibiotic therapy within 2 weeks and an absence of pointers suggesting alternative diagnoses. Our aim was to describe the clinical profile and examine the airway cellularity and likely promoters of neutrophilic inflammation in the bronchoalveolar lavage (BAL) of children with PBB compared with chronic cough due to other causes and controls. We explored the innate immune signaling receptors, toll-like receptors (TLR)-2 and TLR-4, as well as relevant effector molecules. A cross-sectional comparison was made of 100 children median age 2.58 years (with either PBB, coughing due to another cause or no cough controls) who underwent flexible bronchoscopy with lavage. BAL was evaluated for airway cytology, microbiology, inflammatory mediators interleukin 8 (IL-8) and active matrix metalloproteinase 9 (MMP-9) and TLR-2 and TLR-4 messenger RNA (mRNA) expression. Children with PBB had marked airway neutrophilia and increased median cytokine levels when compared to those with cough that resolved naturally and no cough controls: IL-8 0.67 versus 0.07 and 0.06 ng/ml (P < 0.005) and active MMP-9 7.25 versus 1.35 and 0.38 ng/ml (P < 0.005). The values for TLR-2 and TLR-4 mRNA expression were significantly elevated in children with PBB when compared to the control group. PBB is a paediatric condition which presents with chronic moist cough and its airway profile is characterized by intense neutrophilic airway inflammation with marked inflammatory mediator response and evidence of innate immune activation.

Topics: Bronchitis; Bronchoalveolar Lavage Fluid; Case-Control Studies; Child; Child, Preschool; Cough; Female; Humans; Infant; Interleukin-8; Leukocytosis; Male; Matrix Metalloproteinase 9; Neutrophils; RNA, Messenger; Toll-Like Receptor 2; Toll-Like Receptor 4

Cryptococcus neoformans (C. neoformans) is a globally distributed fungal pathogen with the potential to cause serious disease, particularly among immune compromised hosts. Exposure to this organism is believed to occur by inhalation and may result in pneumonia and/or disseminated infection of the brain as well as other organs. Little is known about the role of airway epithelial cells in cryptococcal recognition or their ability to induce an inflammatory response.. Immortalized BEAS-2B bronchial epithelial cells and primary normal human bronchial epithelium (NHBE) were stimulated in vitro with encapsulated or acapsular C. neoformans cultivated at room temperature or 37 degrees C. Activation of bronchial epithelial cells was characterized by analysis of inflammatory cytokine and chemokine expression, transcription factor activation, fungal-host cell association, and host cell damage.. Viable C. neoformans is a strong activator of BEAS-2B cells, resulting in the production of the neutrophil chemokine Interleukin (IL)-8 in a time- and dose-dependent manner. IL-8 production was observed only in response to acapsular C. neoformans that was grown at 37 degrees C. C. neoformans was also able to induce the expression of the chemokine CXCL1 and the transcription factor CAAT/enhancer-binding protein beta (CEBP/beta) in BEAS-2B cells. NHBE was highly responsive to stimulation with C. neoformans; in addition to transcriptional up regulation of CXCL1, these primary cells exhibited the greatest IL-8 secretion and cell damage in response to stimulation with an acapsular strain of C. neoformans.. This study demonstrates that human bronchial epithelial cells mediate an acute inflammatory response to C. neoformans and are susceptible to damage by this fungal pathogen. The presence of capsular polysaccharide and in vitro fungal culture conditions modulate the host inflammatory response to C. neoformans. Human bronchial epithelial cells are likely to contribute to the initial stages of pulmonary host defense in vivo.

Topics: Bronchi; Bronchitis; Cells, Cultured; Chemokine CXCL1; Cryptococcus neoformans; Epithelial Cells; Gene Expression Regulation; Humans; Inflammation Mediators; Interleukin-8; Probability; Protein Binding; Reference Values; Reverse Transcriptase Polymerase Chain Reaction; RNA; Sensitivity and Specificity

Gene delivery applications to treat lung diseases are, in some instances, suboptimal due to deleterious host inflammatory reactions. Current DNA plasmids (pDNA) exert toxicity in part via unmethylated CpG motifs that stimulate Toll-like receptor (TLR)9-expressing leukocytes; however, the airway epithelial response has not been well defined. Bronchial epithelial cells (BEAS-2B) were exposed to pDNA complexes and inflammatory mediators were measured. As patients with inflammatory lung disease are susceptible to infectious exacerbations, we also evaluated the reciprocal inflammatory response to pDNA and bacterial components lipopolysaccharide (LPS) and lipoteichoic acid (LTA), recognized by TLR4 and TLR2, respectively. Cells primed with pDNA synergistically expressed IL-8 mRNA and protein in response to LPS and LTA (3- to 5-fold). A similar induction was also observed for IL-1beta, IL-6, colony-stimulating factor (CSF)-1, and granulocyte macrophage-CSF. Their synergistic elevation was associated with an increase in TLR4 and TLR2 levels. Methylation of pDNA only partially reduced (25-30%) IL-8 release; hence, signaling occurs via CpG/TLR9-dependent and -independent modules. As epidermal growth factor receptor (EGFR) signaling has been implicated in bronchial IL-8 expression, we assessed whether pDNA priming events were coordinated via EGFR. AG1478 (EGFR inhibitor) restored normal TLR4/2 levels and also suppressed synergistic release of IL-8. The extracellular signal-regulated kinase (Erk) mitogen-activated protein kinase inhibitor also blocked IL-8 release, implicating Erk as a key mediator of EGFR signaling. Our findings identify a novel EGFR-dependent mechanism for regulating TLR, and show that targeted disruption of EGFR signaling ameliorates the airway epithelial inflammatory response to pDNA. Targeting the EGFR system may improve the efficiency, tolerability, and safety of gene therapy strategies.

Topics: Bronchitis; Cell Line; CpG Islands; DNA; DNA Methylation; ErbB Receptors; Gene Transfer Techniques; Genetic Therapy; Genetic Vectors; Humans; Interleukin-8; Liposomes; Plasmids; Polymerase Chain Reaction; Respiratory Mucosa; Toll-Like Receptor 2; Toll-Like Receptor 4

Airway inflammation in cystic fibrosis (CF) is exaggerated and characterized by neutrophil-mediated tissue destruction, but its genesis and mechanisms remain poorly understood. To further define the pulmonary inflammatory response, we conducted a proteome-based screen of bronchoalveolar lavage fluid (BALF) collected from young children with and without CF experiencing endobronchial infection.. We collected BALF samples from 45 children younger than 5 years and grouped them according to the presence of respiratory pathogens: > or = 1 x 10(5) colony-forming units (CFU)/mL BALF (18 and 12 samples with and without CF, respectively) and <1 x 10(5) CFU/mL (23 and 15 samples). BALF proteins were analyzed with SELDI-TOF mass spectrometry (MS) and H4 ProteinChips. Proteins were identified and characterized using trypsin digestion, tandem MS, Fourier transform ion cyclotron resonance MS, immunoblotting, and ELISA.. The SELDI-TOF MS BALF profiles contained 53 unique, reliably detected proteins. Peak intensities of 24 proteins differed significantly between the CF and non-CF samples. They included the neutrophil proteins, alpha-defensin 1 and 2, S100A8, S100A9, and S100A12, as well as novel forms of S100A8 and S100A12 with equivalent C-terminal deletions. Peak intensities of these neutrophil proteins and immunoreactive concentrations of selected examples were significantly higher in CF than non-CF samples.. Small neutrophil-derived BALF proteins, including novel C-terminal truncated forms of S100A proteins, are easily detected with SELDI-TOF MS. Concentrations of these molecules are abnormally high in early CF lung disease. The data provide new insights into CF lung disease and identify novel proteins strongly associated with CF airway inflammation.

Topics: Bronchitis; Bronchoalveolar Lavage Fluid; Child, Preschool; Colony Count, Microbial; Cystic Fibrosis; Female; Humans; Infant; Interleukin-8; Leukocyte Count; Male; Neutrophils; Proteome; S100 Proteins; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Gastroesophageal reflux (GER) may induce respiratory symptoms (RS) through inhalation of acid gastric contents. To characterize the airway inflammation associated with this condition, 20 children [7.4 (0.9) yr old] with "difficult to treat" RS and a positive 24-h oesophageal pH monitoring (pHm) were studied and bronchoalveolar lavage (BAL) performed. The control group included 10 children [7.3 (1.3) yr], non-atopics, with a respiratory clinical history similar to the cases but no reflux, as demonstrated by a negative 24-h oesophageal pHm. On BAL samples, in addition to inflammatory indexes, the lipid-laden macrophage (LLM) index was determined as index of gastric content inhalation. As compared to controls, GER children had higher neutrophil proportion (P=0.002), higher LLM index (P=0.004) and higher concentrations of interleukin (IL)-8 (P=0.005), myeloperoxidase (MPO) (P=0.001) and elastase (P=0.045) in BAL fluid. In GER children, but not in controls, neutrophil proportion significantly correlated with LLM index (r=0.65, P=0.002), with IL-8 (r=0.62, P=0.003) and MPO levels (r=0.54, P=0.014) but not with elastase concentrations. These results suggest an active pathogenetic role of IL-8 in the recruitment and activation of neutrophils in the airways of children with GER, respiratory symptoms and BAL findings suggestive of gastric content aspiration.

Topics: Asthma; Bronchitis; Bronchoalveolar Lavage Fluid; Child; Enzyme-Linked Immunosorbent Assay; Female; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Interleukin-8; Leukocytosis; Male; Neutrophil Activation; Neutrophils; Peroxidase; Respiratory Function Tests

Severe alpha-1-antitrypsin deficiency (AATD), due to homozygosity for the protease inhibitor (Pi) Z allele, is a genetic risk factor for chronic obstructive pulmonary disease (COPD). In a previous study the sputum of severe AATD subjects with airflow obstruction showed a pattern of cellular inflammation similar to COPD patients. It is uncertain whether heterozygotes for the Z allele or intermediate deficiency (PiMZ) have an increased risk of developing COPD.. Sputum cell counts and the supernatant level of the neutrophil chemoattractant interleukin (IL)-8 were investigated by sputum induction in 10 non-smoker asymptomatic PiMZ subjects with normal pulmonary function, 10 patients with stable COPD, and 10 age matched normal subjects. Data are expressed as mean (SD).. The mean (SD) number of neutrophils was significantly higher (p<0.01) in the sputum of PiMZ subjects (84.5 (22.2) x10(4)/ml) and patients with COPD (126.9 (18.8) x10(4)/ml) than in matched normal subjects (55.0 (8.7) x10(4)/ml). IL-8 levels were increased in PiMZ subjects (828.5 (490.6) ng/ml; median 1003.0 ng/ml; range 1260-100 ng/ml) and in COPD patients (882.5 (524.3) ng/ml; median 934.9 ng/ml; range 1506-258 mg/ml) compared with normal subjects (3.5 (0.5) ng/ml; median 3.5 ng/ml; range 4.5-2.5 ng/ml). There was a significant positive correlation between IL-8 supernatant concentration and neutrophil count in PiMZ subjects (p = 0.036; r = 0.66). An inverse correlation was observed between the percentage of neutrophils and forced expiratory volume in 1 second (% predicted) in patients with COPD (p = 0.04; r = -0.43).. These findings indicate that PiMZ subjects without airflow obstruction may have an IL-8 related neutrophilic inflammation in the airways, similar to stable COPD patients, suggesting an increased risk of developing pulmonary changes.

Topics: Aged; alpha 1-Antitrypsin Deficiency; Bronchitis; Carbon Monoxide; Case-Control Studies; Female; Forced Expiratory Volume; Humans; Interleukin-8; Leukotriene B4; Male; Middle Aged; Neutrophils; Sputum; Vital Capacity

Acute lung injury (ALI) and its extreme manifestation the acute respiratory distress syndrome (ARDS) complicate a wide variety of serious medical and surgical conditions. Thioredoxin is a small ubiquitous thiol protein with redox/inflammation modulatory properties relevant to the pathogenesis of ALI. We therefore investigated whether thioredoxin is raised extracellulary in patients with ALI and whether the extent of any increase is dependent upon the nature of the precipitating insult.. Bronchoalveolar lavage (BAL) fluid and plasma samples were collected from patients with ALI (n=30) and healthy controls (n=18, plasma; n=14, BAL fluid). Lung tissue was harvested from a separate group of patients and controls (n=10). Thioredoxin was measured by ELISA in fluids and by immunohistochemistry in tissue. Interleukin (IL)-8 levels were determined by ELISA. Disease severity was assessed as APACHE II and SOFA scores.. BAL fluid levels of thioredoxin were higher in patients with ALI than in controls (median 61.6 ng/ml (IQR 34.9-132.9) v 16.0 ng/ml (IQR 8.9-25.1), p<0.0001); plasma levels were also significantly higher. When compared with controls, sections of wax embedded lung tissue from patients with ALI showed greater positive staining for thioredoxin in alveolar macrophages and type II epithelial cells. BAL fluid levels of thioredoxin correlated with IL-8 levels in BAL fluid but not with severity of illness scores or mortality. BAL fluid levels of thioredoxin, IL-8, and neutrophils were significantly greater in patients with ALI of pulmonary origin.. Extracellular thioredoxin levels are raised in patients with ALI, particularly of pulmonary origin, and have a significant positive association with IL-8. Extracellular thioredoxin levels could provide a useful indication of inflammation in ALI.

Topics: Acute Disease; Adult; Autopsy; Biopsy; Bronchitis; Bronchoalveolar Lavage Fluid; Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Female; Humans; Immunohistochemistry; Interleukin-8; Male; Middle Aged; Respiratory Distress Syndrome; Thioredoxins

A study was undertaken to assess both oxidative stress and inflammation in the lungs of patients with chronic obstructive pulmonary disease (COPD) during severe and very severe exacerbations compared with those with stable COPD, healthy smokers, and non-smokers. Two sites within the lungs were compared: the large airways (in sputum) and the peripheral airways (by bronchoalveolar lavage (BAL)).. BAL fluid cell numbers and levels of tumour necrosis factor (TNFalpha) and interleukin (IL)-8 were measured as markers of airway inflammation and glutathione (GSH) levels as a marker of antioxidant status. Nuclear translocation of the pro-inflammatory transcription factors nuclear factor-kappaB (NF-kappaB) and activator protein 1 (AP-1) were also measured by electromobility shift assay in BAL fluid leucocytes and lung biopsy samples.. Influx of inflammatory cells into the peripheral airways during exacerbations of COPD was confirmed. Increased IL-8 levels were detected in BAL fluid from patients with stable COPD compared with non-smokers and healthy smokers, with no further increase during exacerbations. In contrast, IL-8 levels in the large airways increased during exacerbations. GSH levels were increased in the BAL fluid of smokers (444%) and patients with stable COPD (235%) compared with non-smokers and were reduced during exacerbations (severe 89.2%; very severe 52.3% compared with stable COPD). NF-kappaB DNA binding in BAL leucocytes was decreased in healthy smokers compared with non-smokers (41.3%, n = 9, p<0.001) but did not differ in COPD patients, whereas AP-1 DNA binding was significantly decreased during exacerbations of COPD.. There is evidence of increased oxidative stress in the airways of patients with COPD that is increased further in severe and very severe exacerbations of the disease. This is associated with increased neutrophil influx and IL-8 levels during exacerbations.

Topics: Bronchitis; Bronchoalveolar Lavage Fluid; Electrophoretic Mobility Shift Assay; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin-8; Male; Middle Aged; NF-kappa B; Oxidative Stress; Pulmonary Disease, Chronic Obstructive; Tumor Necrosis Factor-alpha

Cystic fibrosis (CF) airways are characterised by chronic inflammation, increased interleukin (IL)-8 secretion, and neutrophil activation which are considered the principal factors of morbidity and mortality in CF patients. Optimising management of this chronic inflammatory response is therefore a key issue of basic and clinical CF research. Several reports have addressed ways to manage CF airways inflammation, and an attractive therapeutic strategy may be the inhibition of the p38-mitogen activated protein kinase (p38-MAP-k) pathway.. A new ex vivo model was used to study the mucosal inflammatory response to environmental airways stimuli. Nasal biopsy tissues from CF patients and controls were cultured ex vivo for 20 minutes, 4 hours, and 24 hours in the presence of lipopolysaccharide (LPS) from Pseudomonas aeruginosa (PA) with and without the p38-MAP-k inhibitor SB203580. Quantitative mRNA assessment, immunohistochemistry, and Western blots were used to detect the expression and modulation of inflammatory markers.. PA-LPS challenge induced a time dependent mucosal inflammation indicated by rapid epithelial activation, IL-8 release, COX-2 upregulation, and neutrophil migration to the upper mucosal layers. Some of these LPS induced changes (IL-8 release and neutrophil migration) were specific to CF tissues. SB203580 significantly controlled all LPS induced mucosal changes in CF tissues.. These findings provide a rationale and proof of principle for the potential use of p38-MAP-k inhibitors to control inflammation in patients with CF.

Topics: Adolescent; Adult; Blotting, Western; Bronchitis; Cells, Cultured; Cyclooxygenase 2; Cystic Fibrosis; Female; Humans; Interleukin-8; Lipopolysaccharides; Male; Membrane Proteins; p38 Mitogen-Activated Protein Kinases; Prostaglandin-Endoperoxide Synthases; Pseudomonas aeruginosa; Respiratory Mucosa; RNA, Messenger

To determine the role of respiratory epithelial cells in the inflammatory response to inhaled endotoxin, we selectively inhibited NF-kappa B activation in the respiratory epithelium using a mutant I kappa B-alpha construct that functioned as a dominant negative inhibitor of NF-kappa B translocation (dnI kappa B-alpha). We developed two lines of transgenic mice in which expression of dnI kappa B-alpha was targeted to the distal airway epithelium using the human surfactant apoprotein C promoter. Transgene expression was localized to the epithelium of the terminal bronchioles and alveoli. After inhalation of LPS, nuclear translocation of NF-kappa B was evident in bronchiolar epithelium of nontransgenic but not of transgenic mice. This defect was associated with impaired neutrophilic lung inflammation 4 h after LPS challenge and diminished levels of TNF-alpha, IL-1 beta, macrophage inflammatory protein-2, and KC in lung homogenates. Expression of TNF-alpha within bronchiolar epithelial cells and of VCAM-1 within peribronchiolar endothelial cells was reduced in transgenic animals. Thus targeted inhibition of NF-kappa B activation in distal airway epithelial cells impaired the inflammatory response to inhaled LPS. These data provide causal evidence that distal airway epithelial cells and the signals they transduce play a physiological role in lung inflammation in vivo.

Topics: Administration, Inhalation; Animals; Bronchi; Bronchitis; Cell Line; Cytokines; Genes, Dominant; Humans; I-kappa B Proteins; Interleukin-8; Lipopolysaccharides; Lung; Mice; Mice, Inbred C57BL; Mice, Transgenic; Mutation; NF-kappa B; NF-KappaB Inhibitor alpha; Peroxidase; Pneumonia; Promoter Regions, Genetic; Pulmonary Alveoli; Pulmonary Surfactant-Associated Protein C; Respiratory Mucosa

Chronic bronchitis is a frequent underlying disease in community-acquired pneumonia (CAP). It is unclear to what extent an impaired or exaggerated innate immune response contributes to disease manifestations and severity. To assess the role of neutrophil activation and recruitment during acute pneumonic episodes, peripheral polymorphonulcear neutrophil (PMN) activation, chemotactic activity, interleukin-8 (CXCL-8) and CXCL-8 receptor (CXCR) expression and apoptosis rate were evaluated in CAP patients with and without chronic bronchitis. In addition, the expression of CXCRs and CXCL-8 was assessed on pulmonary neutrophils in chronic bronchitis patients to compare the activation of the chemokine system in different compartments. CAP severity was assessed by the simplified acute physiology score II and the prognosis of disease was assessed by the pneumonia severity index (PSI). An increased chemotactic activity of PMN from chronic bronchitis patients with CAP was found, which was not related to the expression of CXCRs. In addition, a decreased apoptosis rate of PMN was observed. Chemotactic activity was related to the PSI. Comparison of peripheral and pulmonary PMN revealed enhanced CXCL-8 levels and a decreased CXCR expression in the lung. In conclusion, neutrophil function in patients with chronic bronchitis and community-acquired pneumonia is characterised by an increased chemotactic activity combined with a decreased apoptosis rate. The downregulation of interleukin-8 receptors in the pulmonary compartment deserves further investigation.

Topics: Aged; Apoptosis; Bronchitis; Chemotaxis, Leukocyte; Chronic Disease; Community-Acquired Infections; Female; Humans; Interleukin-8; Male; Neutrophils; Pneumonia; Receptors, Interleukin-8B

To investigate the protective effects of beta-carotene in rats against the development of chronic bronchitis induced by cigarette smoking.. Forty-two Male Wistar rats were randomly divided into three study groups: (1) control (n = 15), animals underwent no treatment; (2) cigarette smoking (n = 15), animals developed chronic bronchitis through long-term cigarette smoking twice a day for 75 d; (3) beta-carotene plus cigarette smoking animals (n = 12) were given 1 ml or 15 mg/kg beta-carotene orally every day just before cigarette smoking. The levels of IL-6, IL-8, NO, superoxide dismutase (SOD) and lipoperoxide (LPO) in serum, bronchoalveolar lavage fluid (BALF) and lung tissue were measured and the pathological changes to lung tissue were analyzed using light microscopy.. Long-term cigarette smoking caused an obvious increase in the amount of IL-6, IL-8 and LPO and a sharp decrease in the levels of NO and SOD in smoking animals compared to controls. beta-carotene intake reversed all the changes induced by smoking and alleviated the pathological changes caused by chronic bronchitis.. Quantitative oral intake of beta-carotene had protective effects against chronic bronchitis induced by long-term cigarette smoking, which was associated with the increased production of NO, the clearance of some oxidative free radicals (OFR) and the alleviation of chronic inflammation.

Topics: Animals; beta Carotene; Bronchitis; Interleukin-6; Interleukin-8; Male; Nitric Oxide; Rats; Rats, Wistar; Smoking; Superoxide Dismutase

To study the clinical features and airway inflammation in eosinophilic bronchitis (EB) and the treatment outcomes.. Irwin's anatomic protocol for diagnosing chronic cough was used in 86 patients with chronic cough, and induced sputum by hypertonic saline aerosol inhalation was performed. Differential cell counts were performed in induced sputum, and eosinophilic cationic protein (ECP) was measured with fluoroimmunoassay, while interleukin-8 (IL-8) was measured with enzyme-linked absorbed immunoassay. EB was diagnosed according to Gibson's criteria and treated with inhaled budesonide 200 - 400 micro g twice daily for four weeks, and in some patients oral prednisone 10 - 15 mg/d or methyl-prednisone 8 - 12 mg/d was given for one week.. 13 (15%) out of 86 patients with chronic cough were diagnosed as having EB. Dry cough was the major compliant and all had normal lung function with negative histamine provocation test. The Eos count was 0.1862 +/- 0.1632 and the concentration of ECP (2.53 +/- 2.07) mg/L in induced sputum were significant higher in patients with EB as compared with those normal subjects (P < 0.01). The cough disappeared in all patients at the end of one week of inhaled or orally administered corticosteroids.. EB, an eosinophilic airway inflammation, is one of important causes of chronic cough and responds well to corticosteroid therapy.

Topics: Adolescent; Adult; Aged; Asthma; Blood Proteins; Bronchitis; Cough; Eosinophil Granule Proteins; Eosinophilia; Female; Humans; Interleukin-8; Male; Middle Aged; Ribonucleases

To explore the effects of Zhikuofang, a TCM prescription, and Ofloxacin on the inflammation and cytostatics of the airway model of bronchiectasis.. The airway model of bronchiectasis (AMB) was set up and infused with Ps. Aeruginosa. A comparison between the effects of Zhikuofang and Of loxacin on the AMB was made.. Zhikuofang is better than Ofloxacin in following aspects: lowering the density of inflammation cells in blood, decreasing the volume of tracheal secretion and inhibiting the cytostatics (IL-8 and TNF-alpha) of the trachea tissue, but Ofloxacin is more effective in diminishing the amount of bacteria in trachea flushing liquor. There was no marked difference between them in their histopathy effects on the trachea.. Zhikuofang probably plays antiphlogistic and bacteriostatic effects by inhibiting the IL-8 and TNF-alpha, resisting secretion, decreasing the inflammation cells and resisting inflammation of trachea.

Topics: Animals; Anti-Infective Agents; Bronchiectasis; Bronchitis; Drug Combinations; Drugs, Chinese Herbal; Female; Interleukin-8; Male; Ofloxacin; Phytotherapy; Plants, Medicinal; Pseudomonas Infections; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha

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

Airway inflammation, with recruitment of neutrophils to the airway lumen, results in purulent secretions and a variety of potential adverse consequences for patients with chronic bronchitis and bronchiectasis. We hypothesised that gradations of sputum colour would correlate directly with the myeloperoxidase content of sputum and with various other indicators of the activity and consequences of bronchial diseases.. To test this hypothesis, we quantified sputum colour by reference to a sensitive nine point colour chart and correlated this assessment with indices of a number of inflammatory mediators in sputum.. The results indicate that standardised visual measurements of sputum colour correlated strongly with myeloperoxidase, interleukin 8, leucocyte elastase (both activity and total quantity), sputum volume, protein leak, and secretory leucocyte proteinase inhibitor (p<0.001 for all). In addition, there was a strong direct correlation between leucocyte elastase and both myeloperoxidase (p<0.003) and sputum volume (p<0.001), but a strong negative correlation with secretory leucocyte proteinase inhibitor (p<0.001).. These results indicate that sputum colour graded visually relates to the activity of the underlying markers of bronchial inflammation. The results of this simple visual analysis of sputum provides guidance concerning underlying inflammation and its damaging potential. It also provides a useful scientific tool for improving the monitoring of chronic airways diseases and response to treatment.

Topics: alpha 1-Antitrypsin; Biomarkers; Bronchiectasis; Bronchitis; Cathepsin B; Color; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin-8; Leukocyte Elastase; Leukotriene B4; Male; Middle Aged; Neutrophils; Pancreatic Elastase; Peroxidase; Proteinase Inhibitory Proteins, Secretory; Proteins; Sputum

Neutrophil-dominated inflammation is prominent in the cystic fibrosis (CF) and chronic bronchitis (CB) airways. We assessed the degree of airway inflammation by measuring the sputum concentrations of interleukin (IL)-8, myeloperoxidase (MPO), and deoxyribonucleic acid (DNA). We determined the relationship among the concentrations of these mediators and investigated methodological problems that may be responsible for reported variability in measurements. Sputa obtained from 31 patients were solubilized with phosphate-buffered saline, dithiothreitol (DTT) (0.1% or 1%), or dornase alfa (0.2 mg/mL). The sputum concentration of IL-8 and MPO was measured by enzyme-linked immunosorbent assay (ELISA), and DNA was measured using microfluorimetry. There was a significant relationship among sputum IL-8, MPO, and DNA. For MPO (means +/- SD), CF was 1,392 +/- 771 vs. CB at 75 +/- 65 mcg/mL; P < 0.0001. For IL-8: CF was 239 +/- 154 vs. CB at 121 +/- 108 ng/mL; P = 0.0002. For DNA, CF was 1.707 +/- 1.25 vs. CB at 0.184 +/- 0.272 mg/mL; P < 0.0001. The MPO concentration in CF sputum was approximately double after in vitro treatment with dornase alfa (P < 0.0001). There is a greater concentration of IL-8, MPO, and DNA in CF than in CB sputa. There is a significant relationship among these inflammatory markers in sputum. DNA polymers bind myeloperoxidase in the sputum, and we speculate that treatment with dornase alfa may remove a source of MPO inhibition.

Topics: Adolescent; Adult; Biomarkers; Bronchitis; Child; Cystic Fibrosis; Deoxyribonuclease I; DNA; Expectorants; Female; Humans; Inflammation; Interleukin-8; Male; Peroxidase; Polymers; Recombinant Proteins; Specimen Handling; Sputum

Tachykinins are neuropeptides present in sensory nerves in the lung. Aside from their role as neurotransmitters, these peptides exert pro-inflammatory and protective effects in the airways. Although tachykinins may be released from sensory nerves, there is increasing evidence that they are also produced by non-neuronal cells. The net effect of tachykinins will likely result from relative changes in the levels of tachykinins, tachykinin receptors and tachykinin degrading enzymes. We investigated whether tachykinins might be produced locally in human airway epithelium in vivo, and whether mRNA levels for either tachykinins, their receptors, or for the tachykinin degrading enzyme neutral endopeptidase (NEP) were altered in subjects with chronic bronchitis compared to normals.. We used reverse transcription polymerase chain reaction analysis of brush biopsy samples to detect mRNAs of interest. We then developed a semi-quantitative approach to compare subject groups.. We detected a signal for preprotachykinin A (PPT-A) mRNA as well as for tachykinin receptors and NEP in patients with airways disease and normal subjects. We found a relative 10-fold increase in PPT-A mRNA in smokers with chronic bronchitis, along with similar increases in mRNA for the inflammatory markers intercellular adhesion molecule-1 and interleukin-8. In contrast, NEP and NK1 tachykinin receptor mRNA levels were not different between the groups.. These findings imply that up-regulation of tachykinin production by cells present in the airway epithelium contributes to the pathophysiology of chronic bronchitis.

Topics: Actins; Adult; Aged; Bronchi; Bronchitis; Bronchoscopy; Chronic Disease; Epithelium; Female; Gene Expression; Humans; Intercellular Adhesion Molecule-1; Interleukin-8; Male; Middle Aged; Neprilysin; Protein Precursors; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Smoking; Tachykinins

IL-15 is a T(H)1-related cytokine that shares many biologic activities with IL-2. Both cytokines bind a specific alpha subunit, and they share the same beta and gamma common receptor subunits for signal transduction. IL-15 has recently been shown to be upregulated in T cell-mediated inflammatory disorders, such as rheumatoid arthritis and inflammatory bowel diseases. However, the role and expression of IL-15 in inflammatory lung disease has not been investigated.. In the present study we have evaluated the expression of IL-15 mRNA and protein in bronchial biopsy specimens obtained from patients with sarcoidosis (n = 8), tuberculosis (n = 7), chronic bronchitis (n = 10), and bronchial asthma (n = 8) and compared its expression with that seen in normal control subjects (n = 11).. In situ hybridization and immunocytochemistry were used to detect the number of cells expressing IL-15 mRNA and protein, respectively, within sections of bronchial tissues from all subject groups. In addition, double immunocytochemistry was used to characterize the cellular source of IL-15.. The number of IL-15(+) cells was significantly higher within tissue from patients with sarcoidosis, tuberculosis, and chronic bronchitis compared with that in asthmatic patients and normal control subjects. Similar results were obtained for IL-15 immunoreactivity by using immunohistochemistry. Furthermore, double immunostaining revealed that neutrophils and macrophages are the major source of IL-15.. These results suggest that the expression of IL-15 may be associated with T(H)1-mediated chronic inflammatory diseases of the lung.

Topics: Asthma; Bronchitis; Humans; Immunohistochemistry; Interleukin-15; Interleukin-8; Neutrophils; RNA, Messenger; Sarcoidosis; Th1 Cells; Tuberculosis, Pulmonary

Nitric oxide (NO) is increased in exhaled air of asthmatics. We hypothesized that endogenous NO contributes to airway inflammation and hyperresponsiveness, and that interleukin-8 (IL-8) might be involved in this mechanism. In human transformed bronchial epithelial cells in vitro, NO donors increased IL-8 production dose-dependently. In addition, tumor necrosis factor-alpha (TNF-alpha) plus IL-1beta plus interferon-gamma (IFN-gamma) increased IL-8 in culture supernatant of epithelial cells; the combination of NO synthase (NOS) inhibitors, aminoguanidine (AG) plus N(G)-nitro-L-arginine methyl ester (L-NAME) attenuated the cytokine-induced IL-8 production in epithelial cells. In guinea pigs in vivo, ozone exposure induced airway hyperresponsiveness to acetylcholine and increased neutrophils in bronchoalveolar lavage fluid (BALF), and these changes persisted for at least 5 h. Pretreatment with NOS inhibitors had no effect on airway hyperresponsiveness or neutrophil accumulation immediately after ozone, but significantly inhibited the changes 5 h after ozone. NOS inhibitors also attenuated the increases of nitrite/nitrate levels in BALF and the IL-8 mRNA expression in epithelial cells and in neutrophils in guinea pig airways 5 h after ozone. These results suggest that endogenous NO may play an important role in the persistent airway inflammation and hyperresponsiveness after ozone exposure, presumably partly through the upregulation of IL-8.

Topics: Acetylcholine; Animals; Blotting, Northern; Bronchi; Bronchial Hyperreactivity; Bronchitis; Bronchoalveolar Lavage Fluid; Cells, Cultured; DNA Primers; Enzyme Inhibitors; Enzyme-Linked Immunosorbent Assay; Epithelial Cells; Guanidines; Guinea Pigs; Humans; In Situ Hybridization; Interleukin-8; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase; omega-N-Methylarginine; Ozone; RNA, Messenger

Obliterative bronchiolitis (OB), the most important long-term complication after lung transplantation, is thought to be a manifestation of chronic rejection within the airways, with the hallmarks inflammation and fibroproliferation.. To characterize the inflammatory process in the context of OB we quantified tumor necrosis factor-alpha, interleukin (IL)-8, IL-10, and transforming growth factor (TGF)-beta on the protein and mRNA level in bronchoalveolar lavage fluid samples obtained from patients with bronchiolitis obliterans syndrome (BOS) and without BOS. In addition, bronchial cells sampled by bronchial brushing were analyzed for mRNA expression.. In respiratory epithelial lining fluid (ELF) from BOS patients the protein levels of IL-8 (52.4+/-22.2 vs. 4.4+/-0.9 pg/ml ELF, P<0.005) and TGF-beta (5.6+/-1.9 vs. 0.9+/-0.2 ng/ml ELF, P<0.005) were significantly elevated. In addition, bronchoalveolar lavage fluid cells of BOS patients showed increased expression of TGF-beta (1.13+/-0.44 vs. 0.45+/-0.16, optical density [O.D.]/O.D. glyceraldehyde-3-phosphate dehydrogenase [GAPDH], P=0.11) and IL-8 (0.25+/-0.13 vs. 0.09+/-0.03 O.D/O.D. GAPDH, P=0.53) without the differences reaching statistical significance. In contrast, IL-8 mRNA expression of bronchial cells was significantly higher in the BOS group (0.85+/-0.40 vs. 0.22+/-0.10 O.D./O.D. GAPDH, P<0.05).. We assume that IL-8 and TGF-beta may act as key mediators for airway inflammation and fibroproliferation in the pathogenesis of OB, with bronchial epithelial cells serving as a relevant source of IL-8.

Topics: Adult; Bronchiolitis Obliterans; Bronchitis; Bronchoalveolar Lavage Fluid; Cell Count; Cell Survival; Cytokines; Eosinophils; Heart-Lung Transplantation; Humans; Inflammation Mediators; Interleukin-8; Lymphocytes; Macrophages; Male; Middle Aged; Neutrophils; RNA, Messenger; Transforming Growth Factor beta

The etiologic role of bacterial pathogens isolated from sputum culture in 40 to 50% of acute exacerbations of chronic bronchitis (AECB) is controversial. If bacterial pathogens cause these AECB, they should be associated with greater neutrophilic airway inflammation than pathogen-negative exacerbations.. This hypothesis was tested by comparing levels of interleukin (IL)-8, tumor necrosis factor (TNF)-alpha, and neutrophil elastase (NE) in 81 sputum samples obtained from 45 patients with AECB. Four groups were compared. In the first three groups, nontypable Haemophilus influenzae (n = 20), Haemophilus parainfluenzae (n = 27), and Moraxella catarrhalis (n = 14) were isolated as sole pathogens, respectively. In the fourth group, only normal flora was isolated (n = 20). Paired samples, obtained from individual patients at different times, that differed in their culture results were also compared.. An outpatient research clinic at a Veterans Affairs Medical Center.. These patients were participating in a prospective, longitudinal study of the dynamics of bacterial infection in chronic bronchitis, for which they were seen in the study clinic on a monthly basis as well as when they were experiencing symptoms suggestive of AECB.. None.. H influenzae exacerbations were associated with significantly higher sputum IL-8, TNF-alpha, and NE. M catarrhalis exacerbations demonstrated significantly higher sputum TNF-alpha and NE when compared to pathogen-negative exacerbations. H parainfluenzae-associated exacerbations had an inflammatory profile similar to pathogen-negative exacerbations. Sputum elastase level distinguished bacterial from nonbacterial AECB and correlated with clinical severity of the AECB.. Increased airway inflammation associated with isolation of H influenzae and M catarrhalis supports an etiologic role of these pathogens in AECB.

Topics: Acute Disease; Aged; Aged, 80 and over; Bronchitis; Chronic Disease; Fibrinogen; Haemophilus; Haemophilus influenzae; Humans; Inflammation; Inflammation Mediators; Interleukin-8; Leukocyte Elastase; Longitudinal Studies; Male; Middle Aged; Moraxella catarrhalis; Prospective Studies; Sputum; Tumor Necrosis Factor-alpha

Many of the features of bronchial disease are believed to be caused by damage to the airways by elastase released by recruited neutrophils. There have been few studies of the mechanisms involved and the interrelationships between components of the inflammatory process. We studied secretions from patients with chronic bronchitis in the stable state. We assessed the presence of neutrophils by measuring myeloperoxidase (MPO) activity and active neutrophil elastase (NE). These results were compared with the chemoattractants interleukin-8 (IL-8) and leukotriene B(4) (LTB(4)), the bronchial inhibitor secretory leukoprotease inhibitor (SLPI), and protein leak (sputum/serum albumin ratio). MPO correlated with NE activity (r = 0.68, p < 0.001) and both IL-8 (r = 0.52, p < 0.001) and LTB(4) (r = 0.41, p < 0.001) indicating an association with the chemoattractants. Elastase activity correlated with IL-8 (r = 0.55, p < 0.001) and LTB(4) (r = 0.41, p < 0.001) but negatively with SLPI (r = -0.49, p < 0.001). NE also correlated positively with protein leak (r = 0.36, p < 0.001), suggesting a cause and effect. MPO and protein leak correlated negatively with FEV(1) (percentage of predicted) only in patients with chronic obstructive pulmonary disease (COPD) without alpha(1)-antitrypsin deficiency (r = -0.37, p < 0.001; r = -0.42, p < 0.01, respectively). These complex interactions provide a template for future studies with specific inhibitors or agonists which will clarify the role of individual factors.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Bronchitis; Enzyme-Linked Immunosorbent Assay; Female; Forced Expiratory Volume; Humans; Interleukin-8; Leukocyte Elastase; Leukotriene B4; Male; Middle Aged; Neutrophil Activation; Neutrophils; Proteinase Inhibitory Proteins, Secretory; Proteins; Secretory Leukocyte Peptidase Inhibitor; Serine Proteinase Inhibitors; Serum Albumin; Sputum; Statistics, Nonparametric

Persistent polymorphonuclear neutrophil (PMN) recruitment to airway is thought to be an important component of continuing inflammation and progression of chronic destructive lung diseases. Although chemoattractants are required for the PMN to migrate, the nature of the chemoattractants in the airways has not yet been clarified. We therefore investigated the contribution of interleukin-8 (IL-8) and leukotriene-B4 (LTB4) to the chemotactic activity of lung secretions by inhibiting their activity using a monoclonal antibody to IL-8 and an LTB4 receptor antagonist (LY293111 sodium). Fifty-nine sputum samples obtained from 19 patients with bronchiectasis were studied. In preliminary studies the chemotactic responses to IL-8 and LTB4 were found to be additive, and we were able to remove their contribution independently with the appropriate antibody and antagonist. The chemotactic activity of the secretions was related to the macroscopic appearance (mucoid, mucopurulent, and purulent), and this appeared to be related to an increase in IL-8 contribution. Chemotactic activity was reduced by antibiotic therapy and again that seemed to relate to a reduction in the IL-8 contribution. The contributions of LTB4 were similar among the three types of sputum in varying clinical states. These data suggest that LTB4 and IL-8 are important chemotactic factors in lung secretions from such patients, although IL-8 appears to play a more important role during acute exacerbations. These results may be useful in determining therapeutic strategies for chronic destructive lung diseases in the future.

Topics: Acute Disease; Anti-Bacterial Agents; Antibodies, Monoclonal; Benzoates; Bronchiectasis; Bronchitis; Cell Movement; Chemotactic Factors; Chemotaxis, Leukocyte; Chronic Disease; Disease Progression; Female; Humans; Interleukin-8; Leukotriene B4; Male; Middle Aged; Mucus; Neutrophils; Receptors, Leukotriene B4; Reproducibility of Results; Sputum; Suppuration

Forty healthy young subjects, ages 20 to 49 yr, underwent videobronchoscopy, mucosal biopsy, and bronchial lavage to evaluate the airway inflammation produced by habitual smoking of marijuana and/or tobacco. Videotapes were graded in a blinded manner for central airway erythema, edema, and airway secretions using a modified visual bronchitis index. The bronchitis index scores were significantly higher in marijuana smokers (MS), tobacco smokers (TS), and in combined marijuana/tobacco smokers (MTS), than in nonsmokers (NS). As a pathologic correlate, mucosal biopsies were evaluated for the presence of vascular hyperplasia, submucosal edema, inflammatory cell infiltrates, and goblet cell hyperplasia. Biopsies were positive for two of these criteria in 97% of all smokers and for three criteria in 72%. By contrast, none of the biopsies from NS exhibited greater than one positive finding. Finally, as a measure of distal airway inflammation, neutrophil counts and interleukin-8 (IL-8) concentrations were determined in bronchial lavage fluid. The percentage of neutrophils correlated with IL-8 levels and exceeded 20% in 0 of 10 NS, 1 of 9 MS, 2 of 9 TS, and 5 of 10 MTS. We conclude that regular smoking of marijuana by young adults is associated with significant airway inflammation that is similar in frequency, type, and magnitude to that observed in the lungs of tobacco smokers.

Topics: Adult; Analysis of Variance; Biopsy; Blood Vessels; Bronchitis; Bronchoalveolar Lavage; Bronchoalveolar Lavage Fluid; Bronchoscopy; Evaluation Studies as Topic; Female; Forced Expiratory Volume; Humans; Hyperplasia; Inflammation; Interleukin-8; Leukocyte Count; Male; Marijuana Smoking; Maximal Midexpiratory Flow Rate; Middle Aged; Neutrophils; Pulmonary Edema; Single-Blind Method; Smoking; Sputum; Videotape Recording; Vital Capacity

Topics: Bronchi; Bronchitis; Cell Degranulation; Chronic Disease; Exocrine Glands; Humans; Interleukin-8; Leukocyte Elastase; Metaplasia; Mucus; Neutrophils; Sensory Receptor Cells; Sputum

Chemical exposure may result in respiratory conditions such as chronic bronchitis, bronchial hyperresponsiveness, and chronic airway obstruction. Clinical studies have shown that during the course of disease, cytokine networks are changed. In order to study the relationship between blood cytokines and respiratory symptoms in an occupational setting, we investigated 106 chemical workers during a routine yearly medical examination in 1995. Lung function was measured with flow volume curves and impedance using the forced oscillation technique (FOT). Smoking-status and respiratory symptoms were determined by questionnaires. Cytokines were selected on biological plausibility and measured both in a whole blood assay (TNF-alpha, IL-8) and in serum (IL-4, IL-5, IL-6, IFN-gamma). The hypothesis is that blood levels of TNF-alpha and IL-8 are increased in bronchitis, while serum levels of IL4, IL-5 are increased and IFN-gamma is decreased in asthmatic workers. Spontaneous IL-8 release was significantly higher in workers with bronchitis (P < 0.05) or chronic bronchitis (P < 0.01) compared to workers without those respiratory symptoms, also after correction for age, pack-years, and blood lymphocyte numbers or compared to a matched control group. No correlation was present between specific cytokines and asthmatic symptoms. These data suggest that blood IL-8 may be considered as a useful marker for bronchitis.

Topics: Adult; Biomarkers; Bronchitis; Chemical Industry; Chronic Disease; Cross-Sectional Studies; Humans; Interleukin-8; Male; Middle Aged; Occupational Exposure; Tumor Necrosis Factor-alpha

Nonencapsulated Haemophilus influenzae strains isolated from patients with chronic bronchitis can be divided into those that persist in the lower respiratory tract and those that do not. We tested the hypothesis that persisting and nonpersisting strains differ in the extent to which they activate epithelial cells to produce two potent inflammatory mediators, interleukin (IL)-6 and IL-8. A suspension of 10(7) and 10(8) colony forming units (cfu) x mL(-1) of H. influenzae, persisting and nonpersisting, induced a dose- and time-dependent production of IL-6 and IL-8 by the human pulmonary mucoepidermoid carcinoma-derived cell line H292, but levels of IL-6 were lower after exposure to persisting H. influenzae (p<0.05). IL-8 production showed a similar trend (p<0.02; analysis of variance). H. influenzae bacteria that adhered to H292 cells were equally distributed over persisting and nonpersisting isolates and induced IL-6 and IL-8 levels similar to their nonadhering counterparts. The difference between persisting and nonpersisting H. influenzae was not due to cytotoxic, antimetabolic or antiproliferative effects on H292 cells. Furthermore, pre-exposure of cells to persisting and nonpersisting isolates did not block subsequent IL-1beta-induced IL-6 production. We conclude that persisting clinical isolates induce less interleukin-6 and interleukin-8 in H292 cells than nonpersisting isolates, probably because they excrete lower amounts of a stimulus of H292 cells. The stimulus is heat stable, hydrophilic and nonproteinous and probably not lipopolysaccharide alone. These findings support the suggestion that some strains of Haemophilus influenzae that persist in the airways of patients, may do so because they induce only a weak inflammatory response.

Topics: Analysis of Variance; Anti-Bacterial Agents; Bacterial Adhesion; Bronchitis; Cells, Cultured; Chloramphenicol; Chronic Disease; Colony Count, Microbial; Enzyme-Linked Immunosorbent Assay; Epithelial Cells; Haemophilus influenzae; Humans; Interleukin-6; Interleukin-8; Lung; Species Specificity

In order to test the hypothesis that changes in lung function induced by ozone (O3) are correlated with cellular and biochemical indices of respiratory tract injury/inflammation, we exposed 20 healthy subjects, on separate days, to O3 (0.2 ppm) and filtered air for 4 h during exercise. Symptom questionnaires were administered before and after exposure, and pulmonary function tests (FEV1, FVC, and SRaw) were performed before, during, and immediately after each exposure. Fiberoptic bronchoscopy, with isolated left main bronchus proximal airway lavage (PAL) and bronchoalveolar lavage (BAL; bronchial fraction, the first 10 ml of fluid recovered) of the right middle lobe, was performed 18 h after each exposure. The PAL, bronchial fraction, and BAL fluids were analyzed for the following end points: total and differential cell counts, and total protein, fibronectin, interleukin-8 (IL-8), and granulocyte-macrophage colony-stimulating factor (GM-CSF) concentrations. The study population was divided into two groups, least-sensitive (n = 12; mean O3-induced change in FEV1 = -7.0%) and most-sensitive (n = 8; mean O3-induced change in FEV1 = -36.0%). We found a significant O3 effect on SRaw (p<0.001) and lower respiratory symptoms (p<0.001) for all subjects combined, but no significant differences between the least- and most-sensitive groups. Ozone exposure increased significantly percent neutrophils in PAL (p=0.01); percent neutrophils, total protein, and IL-8 in bronchial fraction (p<0.001, p<0.001, and p<0.01, respectively); and percent neutrophils, total protein, fibronectin, and GM-CSF in BAL (p<0.001, p<0.001, p<0.01, p=0.05, respectively) for all subjects combined; there were no significant differences, however, between least- and most-sensitive groups. Our results indicate that levels of O3-induced symptoms and respiratory tract injury/inflammation were not correlated with the magnitude of decrements in FEV1 and FVC.

Topics: Adult; Airway Resistance; Biopsy; Bronchitis; Bronchoalveolar Lavage Fluid; Bronchoscopy; Cell Count; Female; Fiber Optic Technology; Fibronectins; Forced Expiratory Volume; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Interleukin-8; Leukocyte Count; Male; Neutrophils; Ozone; Physical Exertion; Proteins; Vital Capacity

Interleukin 8 (IL-8) is a chemoattractant cytokine having a distinct target specificity for the neutrophil. However, it was also found to be active on primed eosinophils. IL-8 was measured by enzyme immunoassay in the bronchoalveolar lavage fluid (BALF) of 9 control subjects, 19 asthmatics and 36 chronic bronchitis patients. Its levels were correlated with neutrophil and eosinophil counts as well as levels of myeloperoxidase (MPO) and eosinophil cationic protein in the BALF. Asthmatic and chronic bronchitis patients had elevated levels of IL-8 in comparison with normal subjects. There was no correlation between the severity of asthma or chronic bronchitis and IL-8 levels. In asthmatic subjects there was a correlation between IL-8 and MPO levels (p < 0.0001, Spearman test). There was no significant correlation between eosinophils and IL-8. In chronic bronchitis there was a correlation between IL-8 and MPO levels as well as between IL-8 and neutrophil counts (p < 0.004 and p < 0.0152, respectively, Spearman test). IL-8 is involved in neutrophilic inflammation in asthma and chronic bronchitis, but differences in the IL-8 regulation of neutrophils were observed in both diseases.

Topics: Adolescent; Adult; Aged; Asthma; Bronchitis; Bronchoalveolar Lavage Fluid; Cell Count; Eosinophils; Humans; Interleukin-8; Middle Aged; Neutrophils; Peroxidase; Severity of Illness Index

Increased lung levels of bombesin-related peptides (BRPs) have been described in smokers and in patients with chronic obstructive pulmonary diseases (COPDs). Moreover, previous studies have shown that BRPs are endowed with immunoregulatory activities. The aim of the present study was to assess the in vitro influence of synthetic bombesin on the activity of mononuclear phagocytes obtained from healthy donors and from COPD patients. Bombesin significantly enhanced in vitro phagocytosis of monocytes and alveolar macrophages in both groups of subjects, restoring deficient phagocytosis in a group of COPD patients. Moreover, bombesin stimulated superoxide anion production and interleukin-8 release by peripheral monocytes.

Topics: Aged; Analysis of Variance; Bombesin; Bronchitis; Chronic Disease; Humans; Interleukin-8; Macrophages, Alveolar; Middle Aged; Monocytes; Superoxides

We investigated the interleukin-8 (IL-8) levels and neutrophil numbers in the sputum of 9 elderly patients with lower respiratory tract infections, including Pseudomonas aeruginosa infection, before and after treatment with various antimicrobial agents. The IL-8 levels in sputum supernatants and the neutrophil numbers in sputum smears from 9 patients decreased significantly after the elimination of the causative respiratory pathogens. We also demonstrated that human recombinant IL-8 at a range of 6.25-25 ng/ml significantly enhanced opsonophagocytic killing of P. aeruginosa immunotype-1 strain by human neutrophils in the presence of a serotype-specific anti-lipopolysaccharide monoclonal antibody and fresh normal human serum. These data suggest that the level of IL-8 production in the airways of patients with lower respiratory tract infections is dependent on bacterial densities, and indicate the important role of IL-8 not only in neutrophil migration but also in opsonophagocytic killing of bacteria in the lower respiratory tract.

Topics: Aged; Bacterial Infections; Bronchiectasis; Bronchitis; Bronchopneumonia; Female; Humans; Interleukin-8; Male; Middle Aged; Pneumonia, Bacterial; Pseudomonas aeruginosa; Recombinant Fusion Proteins; Respiratory Tract Infections; Serum Albumin; Sputum

Topics: Bronchitis; Cystic Fibrosis; Haemophilus influenzae; Humans; Interleukin-8; Mucociliary Clearance; Mucous Membrane; Respiratory Tract Infections; Streptococcus pneumoniae

Granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin (IL)-5 or IL-8 have been suggested to play an important role in the pathogenesis of eosinophilic airway inflammation in bronchial asthma or neutrophilic airway inflammation in chronic bronchitis, respectively, However, GM-CSF and IL-8 have biological activities to either eosinophils or neutrophils.. To investigate the contribution of these cytokines to airway inflammation, we compared the cellular differential and immunolocalization of GM-CSF, IL-5 and IL-8 in sputum cells from patients with bronchial asthma and chronic bronchitis.. Cytospins of sputum cells from 12 patients with bronchial asthma and 12 with chronic bronchitis were subjected to cellular differential counting and immuno-cytochemistry with anti-human GM-CSF, IL-5 and IL-8 antibody.. The predominant cells in bronchial asthma were eosinophils and lymphocytes, while those in chronic bronchitis were neutrophils. All cytokines examined were detected in either bronchial asthma or chronic bronchitis, although the percentage of GM-CSF and Il-5 positive cells in bronchial asthma (53.4 +/- 6.0 [mean +/- SEM]% and 9.7 +/- 2.8%, respectively) was significantly higher than that in chronic bronchitis (11.4 +/- 2.5%; P < 0.001 and 1.7 +/- 0.3%; P < 0.007, respectively). In contrast, the percentage of IL-8 positive cells in chronic bronchitis (23.8 +/- 7.0%) was significantly higher than that in bronchial asthma (7.& +/- 1.9%; P < 0.04). The cells positive for IL-5 were lymphocytes in bronchial asthma and chronic bronchitis. The cells positive for GM-CSF in bronchial asthma were predominantly eosinophils, while those in chronic bronchitis were monocytes/macrophages and neutrophils. In contrast, neutrophils are mainly positive for IL-8 in chronic bronchitis, while monocytes/macrophages and bronchial epithelial cells are positive for IL-8 in bronchial asthma.. The immunochemical comparison of GM-CSF and IL-8 localization in sputum cells between bronchial asthma/chronic bronchitis suggests the differential regulation and roles of these cytokines in eosinophilic vs neutrophilic airway inflammation, resulting in the development of different types of airway inflammation.

Topics: Adult; Aged; Aged, 80 and over; Asthma; Bronchitis; Child; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Interleukin-5; Interleukin-8; Male; Middle Aged; Sputum

Bronchial inflammation in chronic bronchitis has not been characterised as well as in asthma. The present study was undertaken to assess whether a characteristic pattern of bronchial inflammatory markers could be found in patients with chronic bronchitis.. Bronchoscopy with bronchial lavage was performed in 42 patients with chronic bronchitis and in 13 healthy controls. Twenty three of the patients had non-obstructive chronic bronchitis and 19 had chronic bronchitis and chronic obstructive pulmonary disease (COPD). Eighteen of the patients with bronchitis had recurrent infective exacerbations and 24 did not. Intrabronchial bacterial cultures were taken with a protected specimen brush.. Increased activity of neutrophils, fibroblasts, and eosinophils was found in the patients with chronic bronchitis as assessed by the levels of myeloperoxidase (MPO) and interleukin-8 (IL-8), hyaluronan, and eosinophil cationic protein (ECP), respectively. The levels of tryptase did not differ from the controls. High correlations were found between the levels of MPO and IL-8, as well as ECP and IL-8. No differences were found between the patients with COPD and those with non-obstructive chronic bronchitis.. Recruitment and activation of both neutrophils and eosinophils seem to be a characteristic of chronic bronchitis. This activation is associated with IL-8. The patients with intrabronchial cultures of Streptococcus pneumoniae had the highest individual levels of MPO, ECP, and IL-8 of all subjects in the study, indicating that colonisation with S pneumoniae could promote bronchial inflammation.

Topics: Adult; Aged; Biomarkers; Blood Proteins; Bronchitis; Bronchoalveolar Lavage Fluid; Chronic Disease; Eosinophil Granule Proteins; Eosinophils; Fibroblasts; Humans; Hyaluronic Acid; Interleukin-8; Lung Diseases, Obstructive; Middle Aged; Neutrophils; Peroxidase; Ribonucleases; Streptococcus pneumoniae

The potential for interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1) to induce neutrophil and mononuclear phagocyte accumulation in the lungs of patients with pulmonary sarcoidosis and idiopathic pulmonary fibrosis (IPF) was investigated. Bronchoalveolar lavage (BAL) fluids from 12 patients with IPF and 15 with sarcoidosis were concentrated by reversed-phase chromatography, and their IL-8 and MCP-1 concentrations assessed by enzyme-linked immunosorbent assay (ELISA), chemotaxis, and enzyme-releasing assays with monocytes and neutrophils. ELISA revealed significantly elevated concentrations of MCP-1 (20.1 ng/mg albumin) in the BAL fluids of patients with pulmonary sarcoidosis and those with IPF (41.8 ng/mg) in comparison to 11 normal individuals (4.24 ng/mg) and 15 patients with chronic bronchitis (CB) (5.16 ng/mg). Similarly, the chemotactic activity for monocytes (MCP-1 equivalent) was strongly increased in patients with sarcoidosis (86.03 ng/mg) as well as in those with IPF (54.47 ng/mg). The chemoattractant activity of normal individuals and CB patients was 7- or 3-fold lower, respectively. Patients with IPF and sarcoidosis also had elevated IL-8 levels (15.5 and 26.0 ng/mg, respectively; normals: 2.14 ng/mg; and CB patients: 4.23 ng/mg) and greater neutrophil chemotaxis (60.25 and 49.68 ng/mg, respectively; normals: 0.35 ng/mg; and CB patients: 11.06 ng/mg). These data suggest that increased levels of both MCP-1 and IL-8 may be characteristic for sarcoidosis or IPF. It appears likely that both of these chemoattractants contribute to the influx of monocytes and neutrophils into the pulmonary alveolus and interstitium in these diseases.

Topics: Adult; Bronchitis; Bronchoalveolar Lavage Fluid; Chemokine CCL2; Chemotactic Factors; Chemotaxis, Leukocyte; Chromatography; Chronic Disease; Cytokines; Enzyme-Linked Immunosorbent Assay; Hexosaminidases; Humans; Interleukin-8; Middle Aged; Monocytes; Neutrophils; Pulmonary Fibrosis; Sarcoidosis, Pulmonary; Sensitivity and Specificity; Severity of Illness Index

Sputum from patients with cystic fibrosis, bronchiectasis, and chronic bronchitis contains neutrophils and neutrophil proteases, which have been implicated in the pathophysiology of mucus hypersecretion in airways. We asked whether interleukin-8 (IL-8), a potent neutrophil chemoattractant, might be involved in recruiting neutrophils into airways of patients with cystic fibrosis, bronchiectasis, and chronic bronchitis. We found significant neutrophil chemotactic activity in sputum obtained from these patients. The IL-8 concentrations that we measured in sputum of patients with cystic fibrosis (7.1 +/- 1.0 x 10(-9) M, mean +/- SE), bronchiectasis (9.6 +/- 2.9 x 10(-9) M), and chronic bronchitis (2.8 +/- 1.0 x 10(-9) M) have been reported to cause significant chemotaxis in vitro and in airways in vivo, whereas concentrations measured in induced sputum from healthy subjects (1.1 +/- 0.3 x 10(-10) M) do not. A monoclonal antibody to IL-8 significantly inhibited the chemotactic activity in patients' sputum by 75-98%, but not in induced sputum from healthy subjects (9%). We conclude that IL-8 is an important chemotactic factor in sputum of patients with cystic fibrosis, bronchiectasis, and chronic bronchitis, and we suggest that IL-8 accounts, at least in part, for neutrophil recruitment into airways of patients with these diseases.

Topics: Adult; Biomarkers; Bronchiectasis; Bronchitis; Chemotaxis, Leukocyte; Chronic Disease; Cystic Fibrosis; Female; Humans; Inpatients; Interleukin-8; Male; Middle Aged; Neutrophils; Outpatients; Reference Values; Sputum