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Biomedical subjects

J L Devalia

Publications and source records attributed to J L Devalia.

At least 55 records · Page 3Linked to original sources
PubMed1995

Regular albuterol, nedocromil sodium, and bronchial inflammation in asthma.

Adult, nonsmoking patients with mild to moderate asthma were randomized to receive 4 mg nedocromil sodium (n = 13), 200 micrograms albuterol (n = 13), or placebo (n = 12) four times daily for 16 wk in a double-blind, double-dummy protocol. Before and after treatment, patients underwent histamine bronchial provocation, followed by fiberoptic bronchoscopy. Bronchial mucosal biopsy tissue and bronchoalveolar lavage fluid were examined in detail. Daily diary cards were kept by each patient. Compared with baseline, the numbers of total (EG1) and activated (EG2) eosinophils, expressed as cells per square millimeter of bronchial biopsy tissue, decreased after treatment with nedocromil sodium (pretreatment: EG1 = 152.2 +/- 42.5 and EG2 = 143.8 +/- 36.8; post-treatment: EG1 = 115.4 +/- 35.1 and EG2 = 104.9 +/- 31.6) and increased after treatment with albuterol (pretreatment: EG1 = 129.3 +/- 28.0 and EG2 = 127.5 +/- 30.2; post-treatment: EG1 = 238.0 +/- 55.0 and EG2 = 211.4 +/- 50.4). Although the changes between the active treatment groups were significantly different (p < 0.05), no such significant differences were found in eosinophil numbers before and after treatment when comparisons were made between either of the active treatment groups and the placebo group. Although not significant, the changes in concentration of eosinophil cationic protein in bronchoalveolar lavage reflected the changes seen in numbers of activated eosinophils. No treatment differences were detected for mast cell or lymphocyte numbers. There were no statistical differences between treatment groups for clinical findings, with the exception of evening peak flow, which was significantly increased (p < 0.05) in the albuterol group.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1995

The effect of conditioned medium from cultured human bronchial epithelial cells on eosinophil and neutrophil chemotaxis and adherence in vitro.

Several studies have demonstrated that bronchial epithelial cells are capable of synthesizing proinflammatory cytokines that may influence eosinophil and neutrophil activity. We have cultured human bronchial epithelial cells to confluence, as explant cultures, and investigated the effect of conditioned medium from these cells on (1) the chemotaxis of eosinophils and neutrophils and (2) the adherence of these cells to cultured human endothelial cells. Analysis of cytokines, namely interleukin-1 beta (IL-1 beta), interleukin-8 (IL-8), tumor necrosis factor alpha (TNF alpha), granulocyte/macrophage colony-stimulating factor (GM-CSF), and RANTES, which are thought to be involved in these processes, demonstrated that all these cytokines were synthesized and released constitutively from the bronchial epithelial cell cultures. Conditioned medium obtained after 24 h of incubation significantly increased the chemotaxis of eosinophils and neutrophils, from median values of 4.0 cells/per high power field (hpf) (range, 3.0 to 7.0) and 17 cells/hpf (range, 13.0 to 25.0), respectively, for medium 199, to median values of 11.0 cells/hpf (range, 9 to 12; P = 0.005) and 30 cells/hpf (range, 19 to 33; p = 0.01). Whereas anti-GM-CSF and anti-IL-8 neutralizing monoclonal antibodies significantly attenuated the conditioned medium-induced chemotaxis of eosinophils and neutrophils, anti-RANTES neutralizing antibody significantly attenuated the chemotaxis of only eosinophils. Conditioned medium also significantly increased the percentage of eosinophils and neutrophils adhering to endothelial cells in a dose-dependent manner. Both anti-human TNF alpha and anti-human IL-1 beta neutralizing antibodies significantly attenuated the conditioned medium-induced adherence of eosinophils and neutrophils to the endothelial cells and were found to have an additive effect when studied together. Similarly, treatment of endothelial cells with either anti-ICAM-1 or anti-E-selectin, for 1 h before co-culture with eosinophils and neutrophils, significantly attenuated the conditioned medium-induced adherence of both eosinophils and neutrophils to endothelial cells. Treatment of endothelial cells with anti-VCAM-1 attenuated the adherence of eosinophils but not neutrophils. These results suggest that human bronchial epithelial cells, through their ability to generate proinflammatory mediators, are likely to play a role in the pathogenesis of airway disease by influencing chemotaxis and adherence of eosinophils and neutrophils.

Antibodies, Monoclonal↗
PubMed1995

Effect of erythromycin on Haemophilus influenzae endotoxin-induced release of IL-6, IL-8 and sICAM-1 by cultured human bronchial epithelial cells.

Although several studies have demonstrated that low-dose, long-term erythromycin treatment is effective in the management of patients with chronic lower respiratory tract infections, such as chronic bronchitis, bronchiolitis and bronchiectasis, the mechanisms underlying the action of erythromycin are not clear. We have cultured human bronchial epithelial cells (HBEC) as explant cultures from surgical tissue, and have investigated the effect of erythromycin on H. influenzae endotoxin (HIE)-induced release of inflammatory mediators in these cultures. Confluent epithelial cell cultures were incubated with 100 micrograms.mL-1 HIE +/- 0.1-10 micrograms.mL-1 erythromycin and were investigated for interleukin-6 (IL-6), interleukin-8 (IL-8) and soluble intercellular adhesion molecule-1 (sICAM-1) released into the culture medium after 24 h. HIE significantly increased the release of IL-6 from 3.9 +/- 1.5 pg.micrograms-1 cellular protein (in control untreated cultures) to 12.1 +/- 1.5 pg.micrograms-1 cellular protein, and IL-8 from 83.7 +/- 8.2 pg.micrograms-1 cellular protein (in control cultures) to 225.7 +/- 44.8 pg.micrograms-1 cellular protein. Similarly, HIE led to a significantly greater release of sICAM-1 from 0.04 +/- 0.01 ng.microgram-1 cellular protein, in control cultures, to 3.8 +/- 0.9 ng.microgram-1 cellular protein. Incubation of the epithelial cultures in the presence of 0.1-10 micrograms.mL-1 erythromycin significantly blocked the HIE-induced release of IL-6, IL-8, and sICAM-1, at all concentrations of erythromycin investigated. Erythromycin also attenuated neutrophil chemotaxis and adhesion to human endothelial cells, mediated by incubation with conditioned medium obtained from HIE-exposed epithelial cell cultures, in vitro. These results suggest that H. influenzae-induced release of inflammatory mediators from airway epithelial cells could contribute to chronic airway inflammation, and that this effect may be modulated by treatment with erythromycin.

Anti-Bacterial Agents↗
PubMed1994

Effect of nitrogen dioxide and sulphur dioxide on airway response of mild asthmatic patients to allergen inhalation.

Air pollution may enhance the airway response of asthmatic subjects to allergen inhalation. To test the hypothesis that sulphur dioxide and nitrogen dioxide alone or in combination could have a contributory role, we have studied the effect of 6 h exposure to air, 200 parts per billion (ppb) sulphur dioxide, 400 ppb nitrogen dioxide, and the two gases together on the airway response to inhaled allergen in ten volunteers with mild atopic asthma. The subjects were exposed to the gases in random order at weekly visits, then challenged with pre-determined concentrations of Dermatophagoides pteronyssinus allergen 10 min after each exposure. The forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and cumulative breath units (CBU) of D pteronyssinus allergen required to produce a 20% fall in FEV1 (PD20FEV1) were measured after each exposure. Compared with air, neither sulphur dioxide nor nitrogen dioxide nor the combination significantly altered FEV1 or FVC. Although the decreases in PD20FEV1 after exposure to each agent alone were not significant (41.2%, p = 0.125 after nitrogen dioxide; 32.2%, p = 0.506 after sulphur dioxide) the decrease after exposure to the combination was significant (60.5 [SE 8.1]%, p = 0.015). Exposure to a combination of sulphur dioxide and nitrogen dioxide in concentrations that could be encountered in heavy traffic enhances the airway response to inhaled allergen, possibly as a result of previous airway inflammation.

Adult↗
PubMed1994

Effect of inhaled beclomethasone dipropionate on expression of proinflammatory cytokines and activated eosinophils in the bronchial epithelium of patients with mild asthma.

Increasing evidence suggests that cytokines play a role in airway inflammation by attracting and activating inflammatory cells. This may lead to epithelial cell damage and airway hyperresponsiveness. Bronchial provocative concentration of histamine causing a 20% fall in forced expiratory volume in 1 second was measured in patients with mild asthma, and bronchial biopsy specimens were stained for granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-8, and activated eosinophils (EG2) in the bronchial epithelium. The effect of inhaled beclomethasone dipropionate was also assessed in a placebo-controlled double-blind manner. There was a correlation between GM-CSF expression and EG2-staining cells (r = 0.484 p < 0.05) in the epithelium. Provocative concentration of histamine causing a 20% fall in forced expiratory volume in 1 second was correlated with GM-CSF expression (r = -0.462, p < 0.05). Treatment with inhaled beclomethasone dipropionate 500 micrograms twice a day led to a significant decrease in both the expression of GM-CSF (p < 0.01) and IL-8 (p < 0.02) and the number of EG2-staining cells (p < 0.01) in the epithelium. The changes in GM-CSF (r = 0.798, p < 0.01) and IL-8 (r = 0.653, p < 0.02) expression were correlated with the changes in EG2-staining cells after treatment. These results suggest that GM-CSF may influence eosinophil activation in the epithelium in vivo and participate in the etiology of bronchial hyperresponsiveness in mild asthma. Also, beclomethasone dipropionate may inhibit eosinophil activation partly by downregulating the expression of GM-CSF and IL-8 in the bronchial epithelium.

Administration, Inhalation↗
PubMed1994

The impact of pollution on allergic disease.

Evidence suggests that allergic disease is becoming more common, particularly in industrialized societies. Two studies of schoolchildren from Aberdeen, Scotland aged 8-13 years were undertaken in 1964 and 1989 using identical questionnaires, and found that the reported prevalence of asthma had risen from 4.1% to 10.2% during this period, hay fever from 3.2% to 11.9% and eczema from 5.3% to 12%. Indication that air pollution may contribute to this increase has come from several studies. In Japan, allergic rhinoconjunctivitis was found to be more prevalent in individuals living near motorways than in cedar forests. Severe asthma also occurs more commonly than mild asthma in children living in polluted areas. Exercise-induced asthma and the use of asthma medication were twice as high in a town near two power stations compared with a non-polluted town. A recent study in Finland showed that admissions to hospital with severe asthma correlated with atmospheric levels of nitrogen dioxide. Deterioration in peak flow recordings in asthmatics and exacerbations of symptoms in hay fever sufferers correlate with ambient levels of ozone. Elucidation of the mechanisms by which exposure to air pollutants may influence the frequency of allergic disease or exacerbate symptoms has come from in vitro and in vivo experiments in animals and man. Animals exposed to ozone, sulphur dioxide, nitrogen dioxide and particles from diesel exhaust, together with allergens, show more ready development of allergic sensitization compared with those exposed to allergen alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Air Pollution↗
PubMed1994

Effect of Haemophilus influenzae endotoxin on the synthesis of IL-6, IL-8, TNF-alpha and expression of ICAM-1 in cultured human bronchial epithelial cells.

Although studies of infective lung diseases have demonstrated that Haemophilus influenzae is a major pathogen, the mechanisms underlying pathogenesis by this organism are not clear. We have cultured human bronchial epithelial cells (HBEC) to confluency and have investigated the effect of H. influenzae endotoxin (HIE) on: 1) epithelial permeability, by movement of 14C-bovine serum albumin (14C-BSA) across HBEC and measurement of electrical resistance of HBEC; 2) release of interleukin-6 (IL-6), interleukin-8 (IL-8) and tumour necrosis factor-alpha (TNF-alpha) into the supernatant, by enzyme-linked immunosorbent assay (ELISA); and 3) expression of intercellular adhesion molecule-1 (ICAM-1), by immunofluorescence staining. HIE did not significantly increase the movement of 14C-BSA across HBEC. In contrast, HIE progressively increased the electrical resistance of HBEC, such that this was significant after 24 h. Compared with untreated cells, 10-100 micrograms.ml-1 HIE-treated cells released significantly greater amounts of IL-6, IL-8 and TNF-alpha, after 24 h, which was blocked by 10(-5) M hydrocortisone. Similarly, incubation of HBEC with 10-100 micrograms.ml-1 HIE, significantly increased the total number of ICAM-1 positive cells, which were significantly decreased on incubation of the cells in the presence 10(-5) M hydrocortisone. Conditioned medium from HIE-exposed HBEC lead to significant increase in neutrophil chemotaxis and adhesion to endothelial cells in vitro. These results suggest that HIE may affect epithelial cell function and influence inflammation of the airway mucosa via induction of proinflammatory mediators.

Bronchi↗
PubMed1994

No effect of histamine on human bronchial epithelial cell permeability and tight junctional integrity in vitro.

Both animal and human studies have suggested that histamine increases airway epithelial cell permeability in vivo. In order to study the effect of histamine on paracellular epithelial permeability and tight junctional integrity, we have cultured human bronchial epithelial cells to confluency and investigated the effect of topically applied 0.1-20.0 microM histamine. Cultures were established on microporous membranes of tissue culture cell inserts and used for the assessment of: 1) transepithelial movement of radiolabelled mannitol (14C-mannitol) and bovine serum albumin (14C-BSA), in the luminal to serosal direction and 2) changes in electrical resistance of the cultures. Epithelial cell cultures were also established on plastic coverslips, in order to determine tight junction morphology by freeze-fracture electron microscopy, and to assess junctional integrity by lanthanum penetration, using thin sections. Compared with untreated control cultures, 0.1-10 microM histamine did not significantly alter the movement of either 14C-mannitol or 14C-BSA across the epithelial cultures at any time during incubation, but caused an increase in the electrical resistance of the cultures, which was maximal by 6 h of incubation. The morphology of the tight junctions revealed by freeze-fracture and junctional integrity (the latter determined by the degree of lanthanum penetration) were similar in untreated control cultures and cultures incubated with histamine. These studies indicate that histamine does not have a direct effect on paracellular bronchial epithelial permeability in vitro.

Animals↗
PubMed1993

Air pollution and airway epithelial cells.

Recent epidemiological evidence suggests that air pollution, resulting from vehicle exhaust emissions and burning of liquid petroleum gas or kerosene, may play an important role in the development of allergic airways disease. Further, agents such as O3 and NO2 are thought to be major proponents of disease and act by damaging the airway epithelium. It is hypothesised that this pollution-induced damage results in the generation of mediators which lead to inflammation and possibly airway hyperreactivity.

Air Pollutants↗
PubMed1993

Inhibition of human neutrophil migration in vitro by low-molecular-mass products of nontypeable Haemophilus influenzae.

Nontypeable Haemophilus influenzae commonly causes infections in the lower and upper respiratory tract, although the mechanisms of its colonization and persistence in the airways are unclear. Culture filtrates from six clinical isolates of this bacterium were assessed for their abilities to influence neutrophil function in vitro. Each culture filtrate was assessed on six separate occasions with neutrophils obtained from six different donors. During the log and early stationary phases of growth (0 to 18 h), culture filtrates contained primarily neutrophil chemokinetic activity but no activity affecting neutrophil migration toward the chemotactic factors N-formyl-L-methionyl-L-leucyl-L-phenylalanine and leukotriene B4. In contrast, filtrates obtained after 24 h of culture contained factors which inhibited neutrophil migration toward both of these chemotactic factors. This chemotaxis-inhibitory activity persisted between 24 and 72 h of bacterial culture, and it was not associated with the presence of either chemotactic or chemokinetic activity as assessed by checkerboard analysis. Gel filtration of pooled 72-h filtrates yielded three major peaks of chemotaxis-inhibitory activity. Endotoxin was present together with two other low-molecular-mass hydrophobic factors of approximately 8 and 2 kDa. These low-molecular-mass factors are chloroform insoluble and heat stable, and they are inactivated by protease, periodate, and diborane reduction. Activity was completely retained on a wheat germ agglutinin column, and it could be eluted with N-acetyl-D-glucosamine. These data suggest that inhibitory activity is associated with N-acetyl-D-glucosamine-containing glycopeptides, possibly derived from the bacterial cell wall. The production of these compounds may contribute to the persistence of this bacterium in vivo by inhibiting neutrophil chemotaxis in the microenvironment of the respiratory mucosa.

Biological Factors↗
PubMed1993

Effect of nitrogen dioxide on synthesis of inflammatory cytokines expressed by human bronchial epithelial cells in vitro.

Although studies of nitrogen dioxide (NO2) inhalation, in both animals and humans, have demonstrated that this agent can cause epithelial cell damage and inflammation of the airway epithelium, the mechanisms underlying these effects are not well understood. We have cultured human bronchial epithelial cells, as explant cultures from surgical tissue, and studied these firstly from their ability to constitutively synthesize specific proinflammatory cytokines and then investigated the effect of exposure to NO2 on the generation of these cytokines. Constitutive synthesis of cytokines was evaluated by analysis of both the expression of the mRNA for interleukin (IL)-1 beta, IL-4, IL-8, granulocyte/macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma), by the polymerase chain reaction (PCR), and by immunocytochemical staining for the presence of cell-associated IL-1 beta, IL-8, GM-CSF, TNF-alpha, and IFN-gamma, using specific monoclonal and polyclonal antibodies directed towards these cytokines. Release of IL-4, IL-8, GM-CSF, TNF-alpha, and IFN-gamma following exposure to 5% CO2 in air or 400 ppb and 800 ppb NO2 for 6 h was investigated by enzyme-linked immunosorbent assay. PCR demonstrated that the human bronchial epithelial cells expressed the mRNA for IL-1 beta, IL-8, GM-CSF, and TNF-alpha but not for IL-4 and IFN-gamma. Immunocytochemical staining confirmed the presence of endogenous IL-1 beta, IL-8, GM-CSF, and TNF-alpha.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Human bronchial epithelial cell dysfunction following in vitro exposure to nitrogen dioxide.

Nitrogen dioxide (NO2), is a major air pollutant, that causes bronchoconstriction and bronchial hyperreactivity, and may also lead to damage and inflammation of the airway epithelium. We have cultured human bronchial epithelial cells and investigated the effect of exposure to NO2, for 20 min on epithelial cell membrane integrity and function in vitro. Epithelial cell membrane damage and permeability were assessed by release of 51Cr from prelabelled cells, and movement of 14C-labelled bovine serum albumin (BSA) across the bronchial epithelial cell monolayers. Ciliary beat frequency (CBF) of the cells was monitored by the analogue contrast enhancement technique, and arachidonic acid (AA) metabolism was investigated by analysis of radiolabelled AA metabolites generated from cultures prelabelled by incubation with [3H]-arachidonic acid. Exposure to 400 and 800 parts per billion (ppb) NO2 significantly increased the release of 51Cr from 0.9 +/- 0.4%, in control cultures exposed to 5% CO2 in air, to 9.7 +/- 3.2% and 13.9 +/- 3.5%, respectively. Similarly, NO2 also significantly increased the movement of 14C-BSA across the epithelial monolayers from 1.3 +/- 0.2%, in control cultures, to 2.7 +/- 0.2%, 3.8 +/- 0.4% and 5.1 +/- 0.5%, respectively, in cultures exposed to 100, 400 and 800 ppb NO2. Although NO2 attenuated the CBF of the cells at all concentrations investigated, this was significant only at the concentration of 2,000 ppb NO2.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

Topical glucocorticoids inhibit activation by allergen in the upper respiratory tract.

We have studied the effect of a topically administered glucocorticoid, fluticasone propionate (FP), on infiltration and activation of eosinophils in the nasal mucosa after provocation with allergen. Forty-four patients with seasonal allergic rhinitis entered a double-blind, crossover study in which they underwent treatment with either FP (200 micrograms once daily) or identical placebo for 2 weeks. Patients then underwent nasal-allergen provocation followed by nasal lavage and biopsy at one of several time points between 0 and 8 hours. Patients subsequently received the alternate treatment for 2 weeks before repeat allergen provocation, nasal lavage, and biopsy, as before. Biopsy specimens of nasal mucosa obtained during the immediate allergic response demonstrated an influx of eosinophils (stained by monoclonal antibody EG1) of similar magnitude during both FP and placebo treatment. Significantly, fewer eosinophils in these biopsy specimens were activated (stained by monoclonal antibody EG2) after treatment with FP compared with that after placebo treatment (median values, 8.8 and 36.6 cells per square millimeter, respectively; p less than 0.02). The concentration of eosinophil cationic protein in nasal lavage fluid was significantly elevated above baseline from 2 to 8 hours after allergen, and this increase was abolished by treatment with FP. These results suggest that topical glucocorticoids inhibit allergen-induced activation of eosinophils in allergic rhinitis.

Administration, Topical↗
PubMed1992

The effects of salmeterol and salbutamol on ciliary beat frequency of cultured human bronchial epithelial cells, in vitro.

Studies investigating mechanisms of mucociliary clearance have suggested that beta 2-adrenergic agents may significantly influence ciliary activity of epithelial cells and therefore play a vital role in the maintenance of functional integrity of the airways. We have cultured human bronchial epithelial cells, from surgical explants and investigated the effects of salbutamol and salmeterol, in a time- and dose-dependent manner, on the ciliary beat frequency (CBF) of these cells. Prior to and at several times after exposure to either salbutamol (10(-8) to 10(-3) M) or salmeterol (10(-8) to 10(-4) M), the epithelial cells were monitored for CBF and on the basis of data obtained from these studies, the effect of 10(-6) M propranolol was investigated in the presence of optimal concentrations of salbutamol and salmeterol. Salbutamol was optimally active at a concentration of 10(-4) M and caused a transient but significant increase in the CBF from baseline level of 8.6 +/- 0.4 to 9.6 +/- 0.5 Hz (P < 0.05), after 2 h incubation. In contrast, salmeterol was maximally active at a concentration of 10(-6) M and caused a significantly rapid and prolonged increase in CBF from a baseline value of 9.2 +/- 0.4 to 10.9 +/- 0.6 Hz (P < 0.02) and 10.6 +/- 0.8 Hz (P < 0.05) after 15 min and 24 h incubation, respectively. Propranolol (10(-6) M) abrogated the salbutamol- but not the salmeterol-induced increases in CBF.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Agonists↗