scholarly journals High dose vitamin D3 empowers effects of subcutaneous immunotherapy in a grass pollen-driven mouse model of asthma

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Laura Hesse ◽  
N. van Ieperen ◽  
Arjen H. Petersen ◽  
J. N. G. Oude Elberink ◽  
Antoon J. M. van Oosterhout ◽  
...  
Keyword(s):  
Mouse Model ◽  
Grass Pollen ◽  
Airway Hyperresponsiveness ◽  
Allergic Inflammation ◽  
Optimal Dose ◽  
Lavage Fluid ◽  
Subcutaneous Immunotherapy ◽  
High Dose ◽  
Allergen Specific Immunotherapy ◽  
Neutralizing Capacity

AbstractAllergen-specific immunotherapy (AIT) has the potential to provide long-term protection against allergic diseases. However, efficacy of AIT is suboptimal, while application of high doses allergen has safety concerns. The use of adjuvants, like 1,25(OH)2VitD3 (VitD3), can improve efficacy of AIT. We have previously shown that low dose VitD3 can enhance suppression of airway inflammation, but not airway hyperresponsiveness in a grass pollen (GP)-subcutaneous immunotherapy (SCIT) mouse model of allergic asthma. We here aim to determine the optimal dose and formulation of VitD3 for the GP SCIT. GP-sensitized BALBc/ByJ mice received three SCIT injections of VitD3-GP (30, 100, and 300 ng or placebo). Separately, synthetic lipids, SAINT, was added to the VitD3-GP-SCIT formulation (300 nmol) and control groups. Subsequently, mice were challenged with intranasal GP, and airway hyperresponsiveness, GP-specific IgE, -IgG1, and -IgG2a, ear-swelling responses (ESR), eosinophils in broncho-alveolar lavage fluid and lung were measured. VitD3 supplementation of GP-SCIT dose-dependently induced significantly enhanced suppression of spIgE, inflammation and hyperresponsiveness, while neutralizing capacity was improved and ESR were reduced. Addition of VitD3 further decreased Th2 cytokine responses and innate cytokines to allergens in lung tissue by GP-SCIT. However, addition of synthetic lipids to the allergen/VitD3 mixes had no additional effect on VitD3-GP-SCIT. We find a clear, dose dependent effect of VitD3 on GP-SCIT-mediated suppression of allergic inflammation and airway hyperresponsiveness. In contrast, addition of synthetic lipids to the allergen/VitD3 mix had no therapeutic effect. These studies underscore the relevance of VitD3 as an adjuvant to improve clinical efficacy of SCIT treatment regimens.

Timothy grass pollen therapeutic vaccine: optimal dose for subcutaneous immunotherapy

Immunotherapy ◽  
2016 ◽  
Vol 8 (3) ◽  
pp. 251-263 ◽  
Author(s):  
Javier Sola ◽  
José Alberto da Silva Ferreira ◽  
Javier Dionicio Elera ◽  
José Luís Plácido ◽  
Celso Pereira ◽  
...  
Keyword(s):  
Grass Pollen ◽  
Therapeutic Vaccine ◽  
Optimal Dose ◽  
Subcutaneous Immunotherapy ◽  
Timothy Grass ◽  
Timothy Grass Pollen

scholarly journals The Blocking Effect of the Glycoprotein IIb/IIIa Receptor in the Mouse Model of Asthma

2021 ◽  
Author(s):  
Seo-Hee Kim ◽  
Hoang Kim Tu Trinh ◽  
Hae-Sim Park ◽  
Yoo Seob Shin
Keyword(s):  
Mouse Model ◽  
Airway Inflammation ◽  
Airway Hyperresponsiveness ◽  
Inflammatory Cell ◽  
Critical Role ◽  
Allergic Inflammation ◽  
Positive Control ◽  
Blocking Effect ◽  
Histological Evaluation ◽  
Eosinophilic Inflammation

Abstract Background: It is apparent that the interaction between platelets and eosinophils plays a critical role in the activation of allergic inflammation. We investigated whether blocking of the glycoprotein (GP) IIb/IIIa receptor can attenuate allergic inflammation and airway hyperresponsiveness through inhibition of platelet-eosinophil aggregation (PEA) in asthma.Methods: BALB/c mice were sensitized by intraperitoneal injection of ovalbumin (OVA) on days 0 and 14, followed by 3 nebulized OVA challenges on days 28-30. On each challenge day, 5 mg/kg tirofiban was administered intraperitoneally 30 minutes before the challenge. Mice were assessed for airway hyperresponsiveness (AHR), airway inflammation, and the degree of PEA. Finally, the activation levels of platelets and eosinophils were evaluated.Results: Tirofiban treatment decreased AHR and eosinophilic inflammation in BAL fluid. This treatment also reduced the levels of IL-4, IL-5, and IL-13 in BAL fluid and airway inflammatory cell infiltration in histological evaluation. Interestingly, the blocking of the GP IIb/IIIa receptor more reduced PEA in both blood and lung tissue of tirofiban-treated mice than in those of the positive control mice, and both eosinophilic and platelet activations were attenuated in tirofiban-treated mice.Conclusion: The blocking of GP IIb/IIIa receptor with tirofiban can attenuate AHR and airway inflammation through the inhibition of PEA and activation.

scholarly journals The importance of leukotrienes in airway inflammation in a mouse model of asthma.

1996 ◽  
Vol 184 (4) ◽  
pp. 1483-1494 ◽  
Author(s):  
W R Henderson ◽  
D B Lewis ◽  
R K Albert ◽  
Y Zhang ◽  
W J Lamm ◽  
...  
Keyword(s):  
Mouse Model ◽  
Murine Model ◽  
Airway Hyperresponsiveness ◽  
Pulmonary Inflammation ◽  
Late Phase ◽  
Lavage Fluid ◽  
Bronchial Hyperreactivity ◽  
Leukocytic Infiltration ◽  
Specific Inhibitors

Inhalation of antigen in immunized mice induces an infiltration of eosinophils into the airways and increased bronchial hyperreactivity as are observed in human asthma. We employed a model of late-phase allergic pulmonary inflammation in mice to address the role of leukotrienes (LT) in mediating airway eosinophilia and hyperreactivity to methacholine. Allergen intranasal challenge in OVA-sensitized mice induced LTB4 and LTC4 release into the airspace, widespread mucus occlusion of the airways, leukocytic infiltration of the airway tissue and broncho-alveolar lavage fluid that was predominantly eosinophils, and bronchial hyperreactivity to methacholine. Specific inhibitors of 5-lipoxygenase and 5-lipoxygenase-activating protein (FLAP) blocked airway mucus release and infiltration by eosinophils indicating a key role for leukotrienes in these features of allergic pulmonary inflammation. The role of leukotrienes or eosinophils in mediating airway hyperresponsiveness to aeroallergen could not be established, however, in this murine model.

scholarly journals Accelerated Dose Escalation with 3 Injections of an Aluminum Hydroxide-Adsorbed Allergoid Preparation of 6 Grasses Is Safe for Children and Adolescents with Moderate to Severe Allergic Rhinitis

2021 ◽  
pp. 1-11
Author(s):  
Xenia Bovermann ◽  
Isabell Ricklefs ◽  
Christian Vogelberg ◽  
Ludger Klimek ◽  
Matthias V. Kopp
Keyword(s):  
Allergic Rhinitis ◽  
Children And Adolescents ◽  
Aluminum Hydroxide ◽  
Dose Escalation ◽  
Grass Pollen ◽  
High Dose ◽  
Standard Group ◽  
Allergen Specific Immunotherapy ◽  
Strength Group ◽  
The One

A high-dose, accelerated escalation schedule during subcutaneous allergen-specific immunotherapy (AIT) is safe and well-tolerated in adults. However, there are no data in children and adolescents. The aim of the present trial was to assess safety and tolerability of an accelerated dose escalation schedule of an AIT with a grass pollen allergoid in children and adolescents with moderate to severe seasonal rhinoconjunctivitis in a multicenter, open-label, randomized phase II trial. The dose escalation scheme for patients in the One Strength Group included 3 injections with 1 strength B (10,000 TU/mL), whereas the dose escalation scheme for the Standard group included 7 injections with 2 strengths A (1,000 TU/mL) and B (10,000 TU/mL) of an allergoid grass pollen preparation. Overall, <i>n</i> = 50 children (<i>n</i> = 25 in each group; mean age 8.9 + 1.54 years) and <i>n</i> = 37 adolescents (<i>n</i> = 20 and <i>n</i> = 17; 14.2 + 1.62 years) were randomized. For all patients, the mean treatment duration was 59.4 days in the One Strength group and 88.6 days in the Standard group. Treatment-emergent adverse events (TEAEs) related to AIT were reported in 52 and 40% in children and 35 and 35.3% in adolescents, respectively. Systemic allergic reactions occurred in about 5% of our patients and were reported in more patients of the One Strength group (6.7 vs. 2.4%). All systemic reactions were classified as WAO Grade 1. Accelerated high-dose escalation with an aluminum hydroxide-adsorbed grass pollen allergoid can be initiated with a safety and tolerability profile comparable to the standard dose escalation schedule in children and adolescents with allergic rhinitis with or without asthma.

Sequential Development of Airway Hyperresponsiveness and Acute Airway Obstruction in a Mouse Model of Allergic Inflammation

2000 ◽  
Vol 121 (1) ◽  
pp. 57-67 ◽  
Author(s):  
Ulrich Neuhaus-Steinmetz ◽  
Thomas Glaab ◽  
Angelika Daser ◽  
Armin Braun ◽  
Marek Lommatzsch ◽  
...  
Keyword(s):  
Mouse Model ◽  
Airway Obstruction ◽  
Airway Hyperresponsiveness ◽  
Allergic Inflammation ◽  
Sequential Development ◽  
Acute Airway Obstruction

scholarly journals The blocking effect of the glycoprotein IIb/IIIa receptor in the mouse model of asthma

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Seo-Hee Kim ◽  
Hoang Kim Tu Trinh ◽  
Hae-Sim Park ◽  
Yoo Seob Shin
Keyword(s):  
Mouse Model ◽  
Airway Inflammation ◽  
Airway Hyperresponsiveness ◽  
Inflammatory Cell ◽  
Critical Role ◽  
Allergic Inflammation ◽  
Positive Control ◽  
Blocking Effect ◽  
Histological Evaluation ◽  
Eosinophilic Inflammation

Abstract Background It is apparent that the interaction between platelets and eosinophils plays a critical role in the activation of allergic inflammation. We investigated whether blocking of the glycoprotein (GP) IIb/IIIa receptor can attenuate allergic inflammation and airway hyperresponsiveness through inhibition of platelet–eosinophil aggregation (PEA) in asthma. Methods BALB/c mice were sensitized by intraperitoneal injection of ovalbumin (OVA) on days 0 and 14, followed by 3 nebulized OVA challenges on days 28–30. On each challenge day, 5 mg/kg tirofiban was administered intraperitoneally 30 min before the challenge. Mice were assessed for airway hyperresponsiveness (AHR), airway inflammation, and the degree of PEA. Finally, the activation levels of platelets and eosinophils were evaluated. Results Tirofiban treatment decreased AHR and eosinophilic inflammation in Bronchoalveolar Lavage (BAL) fluid. This treatment also reduced the levels of interleukin (IL)-4, IL-5, and IL-13 in BAL fluid and airway inflammatory cell infiltration in histological evaluation. Interestingly, the blocking of the GP IIb/IIIa receptor more reduced PEA in both blood and lung tissue of tirofiban-treated mice than in those of the positive control mice, and both eosinophilic and platelet activations were attenuated in tirofiban-treated mice. Conclusions The blocking of GP IIb/IIIa receptor with tirofiban can attenuate AHR and airway inflammation through the inhibition of PEA and activation.

Therapeutic resolution of late allergic response and airway hyperresponsiveness by Flt-3 ligand in a mouse model of allergic inflammation

2002 ◽  
Vol 109 (1) ◽  
pp. S24-S24
Author(s):  
Jehad H Edwan ◽  
Jennifer Chavez ◽  
Lori Hatcher ◽  
James E Talmadge ◽  
Thomas B Casale ◽  
...  
Keyword(s):  
Mouse Model ◽  
Airway Hyperresponsiveness ◽  
Allergic Inflammation ◽  
Allergic Response

scholarly journals Frequency-dependent airway hyperresponsiveness in a mouse model of emphysema and allergic inflammation

2018 ◽  
Vol 6 (2) ◽  
pp. e13568
Author(s):  
Kentaro Tamura ◽  
Koichiro Matsumoto ◽  
Satoru Fukuyama ◽  
Keiko Kan-o ◽  
Yumiko Ishii ◽  
...  
Keyword(s):  
Mouse Model ◽  
Airway Hyperresponsiveness ◽  
Allergic Inflammation ◽  
Frequency Dependent

scholarly journals Smooth Muscle Hypocontractility and Airway Normoresponsiveness in a Mouse Model of Pulmonary Allergic Inflammation

2021 ◽  
Vol 12 ◽  
Author(s):  
Magali Boucher ◽  
Cyndi Henry ◽  
Alexis Dufour-Mailhot ◽  
Fatemeh Khadangi ◽  
Ynuk Bossé
Keyword(s):  
Smooth Muscle ◽  
Mouse Model ◽  
Airway Hyperresponsiveness ◽  
Inflammatory Cell ◽  
Allergic Inflammation ◽  
Cell Hyperplasia ◽  
Once Daily ◽  
Dust Mite ◽  
Pulmonary Allergic Inflammation

The contractility of airway smooth muscle (ASM) is labile. Although this feature can greatly modulate the degree of airway responsiveness in vivo, the extent by which ASM’s contractility is affected by pulmonary allergic inflammation has never been compared between strains of mice exhibiting a different susceptibility to develop airway hyperresponsiveness (AHR). Herein, female C57BL/6 and BALB/c mice were treated intranasally with either saline or house dust mite (HDM) once daily for 10 consecutive days to induce pulmonary allergic inflammation. The doses of HDM were twice greater in the less susceptible C57BL/6 strain. All outcomes, including ASM contractility, were measured 24 h after the last HDM exposure. As expected, while BALB/c mice exposed to HDM became hyperresponsive to a nebulized challenge with methacholine in vivo, C57BL/6 mice remained normoresponsive. The lack of AHR in C57BL/6 mice occurred despite exhibiting more than twice as much inflammation than BALB/c mice in bronchoalveolar lavages, as well as similar degrees of inflammatory cell infiltrates within the lung tissue, goblet cell hyperplasia and thickening of the epithelium. There was no enlargement of ASM caused by HDM exposure in either strain. Unexpectedly, however, excised tracheas derived from C57BL/6 mice exposed to HDM demonstrated a decreased contractility in response to both methacholine and potassium chloride, while tracheas from BALB/c mice remained normocontractile following HDM exposure. These results suggest that the lack of AHR in C57BL/6 mice, at least in an acute model of HDM-induced pulmonary allergic inflammation, is due to an acquired ASM hypocontractility.

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