Toll-like receptors (TLRs) act as receptors for numerous stimuli of immune cells, including bacterial cell wall constituents (lipopolysaccharide [LPS] from Gram-negative bacteria and lipopeptides from Gram-positive species), plasma proteins and extracellular matrix breakdown products. TLR2 and TLR4 bind lipopeptide and LPS respectively, mediating responses of alveolar macrophages and other immune cells to bacterial infection in the lungs. Exposure of lungs to LPS leads to pro-inflammatory responses of a number of cell types, including airway smooth muscle, which secretes a number of cytokines involved in leucocyte recruitment and the Th2 polarization of immune responses. Human airway smooth muscle cells were cultured with LPS in the absence and presence of peripheral blood mononuclear cells to determine direct and leucocyte-dependent TLR-mediated responses. (more…)
One especially favored target for immune recognition is bacterial lipopolysaccharide (LPS). This macromolecule is found only in ...
Airway hyper-responsiveness in asthma may involve smooth muscle growth, a manifestation of airway remodelling. The involvement ...
Innate immunity depends on both resident and recruited leukocytes. The macrophage without doubt plays an import- ant role in the de ...
Acetylcholine is a neurotransmitter of the nerve vagus, the functional effects mediated by binding to muscarinic receptors. Results ...
Eosinophil infiltration of the mucosa is a feature of asthmatic airways. Their adhesion to bronchial epithelial cells has been ...
Eosinophil infiltration of the mucosa is a feature of asthmatic airways. Their adhesion to bronchial epithelial cells has been proposed to lead to the generation of inflammation mediators which may contribute to asthma pathology. Bronchial epithelial cells (BEAS-2B cell line) and peripheral blood eosinophils were cultured alone or in combination and the production of an inflammatory cytokine, IL-6, was measured. IL-6 was produced principally by epithelial cells and the production was enhanced more than 10-fold in the presence of eosinophils. Significant augmentation of epithelial IL-6 production persisted even when eosinophils were fixed with paraformaldehyde. The eosinophil-induced IL-6 production was extensively inhibited by inhibitors of p38 mitogen-activated protein (MAP) kinase or nuclear factor ??B (NF??B). (more…)
Exacerbations of asthma are frequently associated with rhinoviral infection. Rhinoviruses infect respiratory epithelial cells, ...
Toll-like receptors (TLRs) act as receptors for numerous stimuli of immune cells, including bacterial cell wall constituents (l ...
Airway hyper-responsiveness in asthma may involve smooth muscle growth, a manifestation of airway remodelling. The involvement ...
Contact of pathogens with the innate immune system will most frequently occur at epithelia, and the biology of the airway epitheliu ...
Vascular Endothelial Growth Factor (VEGF), originally described as a vascular permeability factor generating tissue oedema, has be ...
Airway remodelling is considered to be of major importance in the pathology of asthma, with subepithelial basement membrane thickening in particular being indicative of early development of the disease and characteristic of its progression. Airway fibroblasts are central cells in the processes of remodelling: increased deposition of fibroblast-derived connective tissue proteins and differentiation of fibroblasts into contractile myofibroblasts are consistent observations in morphological studies of moderate to severe asthmatic airways. The secretory function of fibroblasts is under the control of locally produced growth factors such as vascular endothelial cell growth factor (VEGF, see below) and platelet-derived growth factor (PDGF). (more…)
Vascular Endothelial Growth Factor (VEGF), originally described as a vascular permeability factor generating tissue oedema, has be ...
Local micro environmental factors are crucial in determining both susceptibility to vascular remodeling and the extent of angio ...
Tumour Necrosis Factor is a pro-inflammatory cytokine implicated in the pathogenesis of asthmatic airway inflammation, hyper-react ...
Asthma is a continuing problem for healthcare, particularly in the industrialized world. Some 150 million people are estimated ...
Airway hyper-responsiveness in asthma may involve smooth muscle growth, a manifestation of airway remodelling. The involvement ...
A role for Leukotriene B4 in the induction of airway hyper-responsiveness was explored through the use of transgenic mice deficient in the BLT1 receptor for LTB4 . Ovalbumin challenge of sensitized wild-type mice resulted in the usual features of experimental asthma, including goblet cell hyperplasia, hyper-responsiveness to inhaled methacholine and elevated BAL fluid concentrations of the Th2 cytokine IL-13. In contrast, BLT1 –/– mice (i.e. genetically modified mice lacking the gene coding for the BLT1 receptor) exhibited significantly lower responses. BLT1 –/– mice also exhibited lower numbers of IL-13-positive T lymphocytes of both the helper (CD4 T Cells) and cytotoxic/suppressor (CD8 + ) types. (more…)
Vascular Endothelial Growth Factor (VEGF), originally described as a vascular permeability factor generating tissue oedema, has be ...
Airway hyper-responsiveness in asthma may involve smooth muscle growth, a manifestation of airway remodelling. The involvement ...
IgE plays an important role in allergic asthma. Reducing IgE in the airway mucosa should reduce airway inflammation. Omalizumab has ...
Some features seem to be common to severe asthma and Chronic Obstructive Pulmonary Disease with reversibility of airflow limita ...
Antihistamines have been shown to be effective in seasonal allergic rhinitis and chronic idiopathic urticaria. They improve qua ...
Despite optimum drug delivery and good compliance with inhaled corticosteroids, many patients experience symptoms and exacerbations. Dose–response studies using inhaled corticosteroids have generally been unable to demonstrate any significant difference between individual doses of inhaled corticosteroids. For example, a metaanalysis evaluated eight studies (2324 asthmatics) where the effects of at least two doses of inhaled fluticasone were measured. (more…)
Current internationally recognized guidelines indicate that symptomatic asthmatics using a low to medium inhaled corticosteroid ...
Leukotrienes can be found in the airway and urine following both spontaneous exacerbations of asthma and acute exposure to bron ...
Treating allergic rhinitis may have a downstream effect on concomitant asthma and this may be due to attenuation of the underlying ...
The guidelines for asthma management recommend the use of regular inhaled corticosteroid in patients with mild persistent asthma, b ...
This study was similar to the study of Harrison and colleagues, which looked at doubling the dose of inhaled corticosteroid dur ...
Treg cells or regulatory T cells constitute a large population of cellular infiltrate in atopic/allergic inflammation and a dysregulated immune response appears to be an important pathogenetic factor. Cardinal events during allergic inflammation can be classified as activation, organ-selective homing, survival and reactivation, and effector functions of immune system cells. T cells are activated by aeroallergens, food antigens, autoantigens, and bacterial exotoxins superantigens in allergic inflammation. They are under the influence of the skin, lung, or nose-related chemokine network and show organ-selective homing. (more…)
Allergen-specific immunotherapy is highly effective in the treatment of IgE-mediated allergy diseases such as rhinitis, conjunc ...
The induction of immune tolerance and specific immune suppression are essential processes in the control of immune responses. R ...
The intracellular forkhead winged transcription factor Foxp3 (forkhead box P3) appears to be specifically expressed by naturall ...
An emerging concept is that pro-inflammatory signals lead to loss of Regulatory T Cells (Treg) function. Pasare and Medzhitov ( ...
Regulatory T cells Treg (picture above) is the existence of suppressor cells, which limit ongoing immune responses and prevent ...
The intracellular forkhead winged transcription factor Foxp3 (forkhead box P3) appears to be specifically expressed by naturally occurring Treg cells, particularly in mice, although in humans there is evidence of upregulation of Foxp3 in all T cells on activation. Foxp3 is required for the development and function of naturally occurring regulatory t cells (treg) and expression is sufficient to convert non-regulatory CD4+CD25T cells into cells with regulatory activity. Conversion of peripheral CD4+CD25 naive T cells to Foxp3+CD4+CD25 foxp3+ Treg cells can be induced by TGF-ß. In a murine asthma model, these TGF-ß-induced Treg prevented house-dust mite-induced allergic pathogenesis or infection pathogenesis in lungs. A single independent report has suggested that IL-4 and IL-13 also induce Foxp3+CD25+ Treg from CD4+CD25precursors. (more…)
Regulatory T cells Treg (picture above) is the existence of suppressor cells, which limit ongoing immune responses and prevent ...
An emerging concept is that pro-inflammatory signals lead to loss of Regulatory T Cells (Treg) function. Pasare and Medzhitov ( ...
Treg cells or regulatory T cells constitute a large population of cellular infiltrate in atopic/allergic inflammation and a dys ...
The induction of immune tolerance and specific immune suppression are essential processes in the control of immune responses. R ...
Allergen-specific immunotherapy is highly effective in the treatment of IgE-mediated allergy diseases such as rhinitis, conjunc ...
A variety of proinflammatory cells, mediators, and cytokines orchestrate the development of airway hyperresponsiveness, which results in the episodic airflow obstruction characteristic of asthma. As a consequence, modulation of the underlying disease process with antii-nflammatory agents is firmly established as being the cornerstone of successful management. Inhaled corticosteroids are the most potent antiinflammatory agents available and satisfactorily suppress underlying airway inflammation in most individuals. (more…)
The cysteinyl leukotrienes (LTC 4 , LTD 4 and LTE 4 ) are lipid mediators produced from an arachidonic acid precursor following ...
Antihistamines have been shown to be effective in seasonal allergic rhinitis and chronic idiopathic urticaria. They improve qua ...
In the UK, Europe and the USA, montelukast is licensed for once-daily oral administration in adults and is also available as a ...
Leukotrienes can be found in the airway and urine following both spontaneous exacerbations of asthma and acute exposure to bron ...
Despite optimum drug delivery and good compliance with inhaled corticosteroids, many patients experience symptoms and exacerbat ...
This study was similar to the study of Harrison and colleagues, which looked at doubling the dose of inhaled corticosteroid during an asthma exacerbation. This study investigated whether doubling the dose of budesonide inhalation in patients on regular inhaled budesonide would be beneficial during an asthma exacerbation. (more…)
The management of asthma in the community involves patient education to avoid the triggers, doubling the dose of inhaled steroi ...
The guidelines for asthma management recommend the use of regular inhaled corticosteroid in patients with mild persistent asthma, b ...
Asthma control is improved by combining inhaled corticosteroids with long acting beta-agonists but patients still require relie ...
This study evaluated budesonide formoterol efficacy and safety of a novel asthma management strategy for both maintenance and s ...
The role of oral and inhaled corticosteroids in the management of acute asthma is well known. This study compared the effects of in ...
Some features seem to be common to severe asthma and Chronic Obstructive Pulmonary Disease with reversibility of airflow limitation. The neutrophil chemoattractant leukotriene B 4 (LTB 4) may play a role in Chronic Obstructive Pulmonary Disease and in some forms of asthma. In this study, 55 smokers with no disease, Chronic Obstructive Pulmonary Disease (with or without bronchodilator reversibility of airflow limitation) or asthma underwent measurement of LTB 4 in sputum supernatants and exhaled breath condensate asthma (EBC). Both Chronic Obstructive Pulmonary Disease and asthma patients had higher levels of LTB 4 than control subjects; patients with asthma or reversible Chronic Obstructive Pulmonary Disease exhibited significantly higher levels of LTB 4 than those with irreversible Chronic Obstructive Pulmonary Disease. (more…)
Leukotrienes are present in increased amounts in exhaled breath condensate (EBC) in patients with asthma. So far, no data have ...
The cysteinyl leukotrienes (LTC 4 , LTD 4 and LTE 4 ) are lipid mediators produced from an arachidonic acid precursor following ...
A role for Leukotriene B4 in the induction of airway hyper-responsiveness was explored through the use of transgenic mice defic ...
Adjusting the inhaled glucocorticoid dose based on indices of airway inflammation has been proposed as a means of achieving more ef ...
With the help of well-trained and experienced pulmonary function technicians, children as young as 4 to 5 years of age should b ...