scholarly journals Airway IL-1β associates with IL-5 production following dust mite allergen inhalation in humans

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Allison J. Burbank ◽  
Stephen A. Schworer ◽  
Amika Sood ◽  
Martha Almond ◽  
Kelly Chason ◽  
...  
Keyword(s):  
Allergen Challenge ◽  
Allergic Airway Inflammation ◽  
Positive Association ◽  
Inflammatory Cells ◽  
Forced Expiratory Volume ◽  
Induced Sputum ◽  
Cytokines And Chemokines ◽  
Dust Mite ◽  
Allergen Inhalation ◽  
Relationship Of

Abstract Background Preclinical studies implicate interleukin (IL)-1β as a key mediator of asthma and have shown the efficacy of IL-1 antagonism for treatment of allergic airway inflammation; human studies in this area are lacking. Objectives Our aim was to study the relationship of airway IL-1β to features of acute allergen-induced asthma exacerbation in humans. Methods Dust mite-allergic adults with mild asthma underwent inhalation challenge with Dermatophagoides farinae. Fractional exhaled nitric oxide (FeNO), induced sputum and peripheral blood samples were obtained pre- and 24 h post-challenge. Spirometry was performed before and throughout the challenge at 10-min intervals, and allergen responsiveness was defined by a 20% fall in Forced Expiratory Volume in 1 s (FEV1). Sputum samples were analyzed for inflammatory cells, cytokines and chemokines. Multiple linear regression was employed to test the association between sputum IL-1β concentration and biomarkers of T helper type 2 (T2)-dominant inflammation. Results Fourteen volunteers underwent inhaled allergen challenge. Allergen responsive volunteers showed a greater positive change in IL-1β in sputum following allergen challenge compared to non-responders. Higher pre-challenge sputum IL-1β was associated with greater increase in sputum IL-5 (p = 0.004), sputum eosinophils (p = 0.001) and blood IL-5 (p = 0.003) following allergen challenge. Allergen-induced sputum IL-1β production was significantly associated with sputum and blood IL-5 (p < 0.001 and p = 0.007, respectively), sputum IL-4 (p = 0.001), IL-13 (p = 0.026), eosinophils (p = 0.008) and FeNO (p = 0.03). Conclusions The positive association between production of IL-1β and biomarkers of T2 inflammation, particularly IL-5, in humans is consistent with work in animal models that demonstrates a link between IL-1β and the pathophysiology of allergic asthma. The role of IL-1β in human asthma warrants further study.

scholarly journals Allergen-Induced Asthma

2014 ◽  
Vol 21 (5) ◽  
pp. 279-282 ◽  
Author(s):  
Donald W Cockcroft
Keyword(s):  
Allergen Challenge ◽  
Airway Disease ◽  
Forced Expiratory Volume ◽  
Lower Airway ◽  
Pharmacological Agents ◽  
The Past ◽  
Dust Mite ◽  
Allergen Inhalation ◽  
Inhalation Challenge ◽  
Allergen Inhalation Challenge

It was only in the late 19th century that specific allergens, pollen, animal antigens and, later, house dust mite, were identified to cause upper and lower airway disease. Early allergen challenge studies, crudely monitored before measurement of forced expiratory volume in 1 s became widespread in the 1950s, focused on the immediate effects but noted in passing prolonged and/or recurrent asthma symptoms. The late asthmatic response, recurrent bronchoconstriction after spontaneous resolution of the early responses occurring 3 h to 8 h or more postchallenge, has been identified and well characterized over the past 50 years. The associated allergen-induced airway hyper-responsiveness (1977) and allergen-induced airway inflammation (1985) indicate that these late sequelae are important in the mechanism of allergen-induced asthma. Allergens are now recognized to be the most important cause of asthma. A standardized allergen inhalation challenge model has been developed and is proving to be a valuable research tool in the investigation of asthma pathophysiology and of potential new pharmacological agents for the treatment of asthma.

The Relationship of Induced-Sputum Inflammatory Cells to BAL and Biopsy

CHEST Journal ◽  
2003 ◽  
Vol 123 (3) ◽  
pp. 371S-372S ◽  
Author(s):  
Philip E. Silkoff ◽  
John B. Trudeau ◽  
Robyn Gibbs ◽  
Sally Wenzel
Keyword(s):  
Inflammatory Cells ◽  
Induced Sputum ◽  
Relationship Of ◽  
The Relationship

scholarly journals Increased Levels of Airway Neutrophils Reduces the Inhibitory Effects of Inhaled Glucocorticosteroids on Allergen-Induced Airway Eosinophils

2002 ◽  
Vol 9 (1) ◽  
pp. 26-32 ◽  
Author(s):  
Gail M Gauvreau ◽  
Mark D Inman ◽  
Margaret Kelly ◽  
Richard M Watson ◽  
Sandra C Dorman ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Negative Relationship ◽  
Allergen Challenge ◽  
Inflammatory Cells ◽  
Induced Sputum ◽  
Atopic Asthma ◽  
Double Blind ◽  
Inhaled Steroids ◽  
Before And After ◽  
Sputum Eosinophils

BACKGROUND: Treatment with inhaled glucocorticosteroids attenuates allergen-induced airway inflammation but is less effective in people with asthma who have noneosinophilic airway inflammation.OBJECTIVE: Studies in which glucocorticosteroid treatment was used before allergen challenges were re-examined to determine whether the efficacy of steroid treatment could be predicted by baseline levels of sputum inflammatory cells.PATIENTS AND METHODS: Twenty-eight nonsmoking subjects with atopic asthma controlled by beta2-agonists participated in only one of three studies, each carried out with a double-blind, placebo controlled, randomized, crossover design. Subjects were treated with glucocorticosteroids or placebo for six to eight days and then underwent allergen inhalation challenge. Spirometry was measured for 7 h after allergen challenge, and then sputum inflammatory cells were measured. Sputum inflammatory cells were also measured before and after treatment, and 24 h after allergen challenge. The per cent inhibition of the allergen-induced airway responses by glucocorticosteroids was calculated.RESULTS: Inhaled gluticocorticosteroids significantly attenuated the early and late asthmatic responses, and the number of allergen-induced sputum eosinophils (P<0.05). There was a significant negative relationship between the number of sputum neutrophils at baseline, and the per cent inhibition of allergen-induced sputum eosinophils measured at 7 h (r=-0.61, P<0.001) and 24 h (r=-0.73, P<0.0001) after challenge, suggesting that glucocorticosteroids are less effective in attenuating allergen-induced airway inflammation in subjects with high levels of neutrophils. There was no correlation between the number of sputum eosinophils at baseline and the per cent inhibition of allergen-induced responses.CONCLUSIONS: Baseline airway neutrophils, not eosinophils, can be used to predict the efficacy of inhaled steroids on allergen-induced sputum eosinophils.

scholarly journals The non-antibiotic macrolide EM900 attenuates HDM and poly(I:C)-induced airway inflammation with inhibition of macrophages in a mouse model

2019 ◽  
Vol 69 (1) ◽  
pp. 139-151 ◽  
Author(s):  
Hironori Sadamatsu ◽  
Koichiro Takahashi ◽  
Hiroki Tashiro ◽  
Go Kato ◽  
Yoshihiko Noguchi ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Bronchoalveolar Lavage Fluid ◽  
Allergic Airway Inflammation ◽  
Inflammatory Cells ◽  
Lavage Fluid ◽  
Poly I:C ◽  
Inhibitory Effects ◽  
Polycytidylic Acid ◽  
Bacterial Drug Resistance ◽  
Dust Mite

Abstract Objective Macrolides have been reported to reduce the exacerbation of severe asthma. The aim of this study was to clarify the effects and mechanisms of EM900, a non-antibiotic macrolide, on allergic airway inflammation. Methods Mice were sensitized and challenged by house dust mite (HDM), then exposed to polyinosinic-polycytidylic acid (poly(I:C)) as a model of asthma complicated with viral infection. Mice were administered with EM900. Airway inflammation was assessed from inflammatory cells in bronchoalveolar lavage fluid (BALF) and cytokines in lung tissues. Lung interstitial macrophages were counted by flow cytometry. Cytokine production, phosphorylation of NF-κB, and p38 in macrophages were examined by ELISA and western blotting. Results Counts of cells in BALF and concentrations of IL-13, IL-5, RANTES, IL-17A, and MIP-2 were significantly decreased by EM900 compared to those without EM900. Percentages of lung interstitial macrophages were significantly decreased with EM900. Concentrations of IL-6, RANTES, and MIP-2 induced by HDM and poly(I:C) were significantly suppressed by EM900 through the suppression of NF-κB and p38 phosphorylation in macrophages. Conclusions HDM and poly(I:C)-induced airway inflammation is attenuated by EM900 with the inhibition of lung interstitial macrophages. Clinical use of EM900 is expected, because EM900 has inhibitory effects against airway inflammation without inducing bacterial drug resistance.

Inflammatory and mechanical factors of allergen-induced bronchoconstriction in mild asthma and rhinitis

2001 ◽  
Vol 91 (3) ◽  
pp. 1029-1034 ◽  
Author(s):  
Emanuele Crimi ◽  
Manlio Milanese ◽  
Susanna Oddera ◽  
Carlo Mereu ◽  
Giovanni A. Rossi ◽  
...  
Keyword(s):  
Allergen Challenge ◽  
Inflammatory Cells ◽  
Mild Asthma ◽  
Bronchial Biopsy ◽  
Membrane Thickness ◽  
Basement Membrane Thickness ◽  
Bronchial Inflammation ◽  
Airway Mechanics ◽  
Allergen Inhalation ◽  
The Difference

We studied whether different bronchial responses to allergen in asthma and rhinitis are associated with different bronchial inflammation and remodeling or airway mechanics. Nine subjects with mild asthma and eight with rhinitis alone underwent methacholine and allergen inhalation challenges. The latter was preceded and followed by bronchoalveolar lavage and bronchial biopsy. The response to methacholine was positive in all asthmatic but in only two rhinitic subjects. The response to allergen was positive in all asthmatic and most, i.e., five, rhinitic subjects. No significant differences between groups were found in airway inflammatory cells or basement membrane thickness either at baseline or after allergen. The ability of deep inhalation to dilate methacholine-constricted airways was greater in rhinitis than in asthma, but it was progressively reduced in rhinitis during allergen challenge. We conclude that 1) rhinitic subjects may develop similar airway inflammation and remodeling as the asthmatic subjects do and 2) the difference in bronchial response to allergen between asthma and rhinitis is associated with different airway mechanics.

Allergen-induced increase in airway responsiveness and inflammation in mild asthma

1990 ◽  
Vol 69 (6) ◽  
pp. 2209-2214 ◽  
Author(s):  
V. Brusasco ◽  
E. Crimi ◽  
P. Gianiorio ◽  
S. Lantero ◽  
G. A. Rossi
Keyword(s):  
Allergen Challenge ◽  
Inflammatory Cells ◽  
Multiple Regression Model ◽  
Airway Responsiveness ◽  
Bronchial Lumen ◽  
History Of ◽  
Allergen Inhalation ◽  
Inhalation Challenge ◽  
Independent Variable ◽  
The Relationship

The relationship between airway responsiveness to methacholine and inflammatory cells in bronchoalveolar lavage (BAL) was determined in patients with history of rhinitis and/or mild bronchial asthma either at baseline (10 patients) or 3-4 h after allergen inhalation challenge (11 patients). At baseline, airway responsiveness did not correlate with any BAL cell population. When data obtained after allergen challenge were included in the analysis, 44% of the variability of airway responsiveness was explained by a multiple regression model with BAL eosinophils as a directly correlated (P = 0.002) independent variable and with BAL macrophages as an inversely correlated (P = 0.045) independent variable. Changes in airway responsiveness after allergen challenge were predicted (82% of variance explained) by a model with BAL eosinophils and BAL lymphocytes as directly correlated (P = 0.0002 and P = 0.03, respectively) independent variables. We conclude that, in stable asymptomatic asthma, baseline airway responsiveness does not correlate with the presence in the airways of inflammatory and immunoeffector cells that can be recovered by BAL. Nevertheless the allergen-induced increase in airway responsiveness is associated with an influx of eosinophils and lymphocytes in the bronchial lumen.

scholarly journals Loss of IL-33 enhances elastase-induced and cigarette smoke extract-induced emphysema in mice

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Daisuke Morichika ◽  
Akihiko Taniguchi ◽  
Naohiro Oda ◽  
Utako Fujii ◽  
Satoru Senoo ◽  
...  
Keyword(s):  
Cigarette Smoke ◽  
Intratracheal Instillation ◽  
Inflammatory Cells ◽  
Cigarette Smoke Extract ◽  
Lymphoid Cells ◽  
Chronic Obstructive ◽  
Porcine Pancreas ◽  
Obstructive Pulmonary Disease ◽  
Quantitative Morphometry ◽  
Cytokines And Chemokines

Abstract Background IL-33, which is known to induce type 2 immune responses via group 2 innate lymphoid cells, has been reported to contribute to neutrophilic airway inflammation in chronic obstructive pulmonary disease. However, its role in the pathogenesis of emphysema remains unclear. Methods We determined the role of interleukin (IL)-33 in the development of emphysema using porcine pancreas elastase (PPE) and cigarette smoke extract (CSE) in mice. First, IL-33−/− mice and wild-type (WT) mice were given PPE intratracheally. The numbers of inflammatory cells, and the levels of cytokines and chemokines in the bronchoalveolar lavage (BAL) fluid and lung homogenates, were analyzed; quantitative morphometry of lung sections was also performed. Second, mice received CSE by intratracheal instillation. Quantitative morphometry of lung sections was then performed again. Results Intratracheal instillation of PPE induced emphysematous changes and increased IL-33 levels in the lungs. Compared to WT mice, IL-33−/− mice showed significantly greater PPE-induced emphysematous changes. No differences were observed between IL-33−/− and WT mice in the numbers of macrophages or neutrophils in BAL fluid. The levels of hepatocyte growth factor were lower in the BAL fluid of PPE-treated IL-33−/− mice than WT mice. IL-33−/− mice also showed significantly greater emphysematous changes in the lungs, compared to WT mice, following intratracheal instillation of CSE. Conclusion These observations suggest that loss of IL-33 promotes the development of emphysema and may be potentially harmful to patients with COPD.

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