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

Neuhaus-Steinmetz, Ulrich; Glaab, Thomas; Daser, Angelika; Braun, Armin; Lommatzsch, Marek; Herz, Udo; Kips, Johan; Alarie, Yves; Renz, Harald

doi:10.1159/000024298

Cited by 78 publications

(82 citation statements)

References 26 publications

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“…Measurements of airway responsiveness were performed 24 h after the last challenge (day 59) by head-out body plethysmography as previously described [24]. Airflow signals were recorded in response to methacholine (0, 12.5, 25, 50, 100, 200 mg/ml) and aerosolized with a nebulizer.…”

Section: Methodsmentioning

confidence: 99%

Intranasal Treatment with a Recombinant Hypoallergenic Derivative of the Major Birch Pollen Allergen Bet v 1 Prevents Allergic Sensitization and Airway Inflammation in Mice

Wiedermann¹,

Herz

Baier³

et al. 2001

Int Arch Allergy Immunol

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Background: The major birch pollen allergen Bet v 1 represents one of the most prevalent environmental allergens responsible for allergic airway inflammation. Objective: In the present study we sought to compare the complete recombinant Bet v 1 allergen molecule with genetically produced hypoallergenic fragments of Bet v 1 regarding mucosal tolerance induction in a mouse model of allergic asthma. Methods: BALB/c mice were intranasally treated with recombinant Bet v 1 or with two recombinant Bet v 1 fragments (F I: aa 1–74; F II: aa 75–160) prior to aerosol sensitization with birch pollen and Bet v 1. Results: Intranasal application of F II, containing the major T cell epitope, led to significant reduction of IgE/IgG1 antibody responses, in vitro cytokine production (IL-5, IFN-γ, IL-10) and negative immediate cutaneous hypersensitivity reactions comparable to the pretreatment with the complete rBet v 1 allergen. Moreover, airway inflammation (eosinophilia, IL-5) was inhibited by the pretreatment with either the complete Bet v 1 or F II. However, for prevention of airway hyperresponsiveness the complete molecule was required. The mechanisms leading to immunosuppression seemed to differ in their dependence on the conformation of the molecules, since tolerance induced with the complete Bet v 1, but not with F II, was transferable with spleen cells and associated with increased TGF-β mRNA levels. Conclusion: We conclude that mucosal tolerance induction with recombinant allergens and genetically engineered hypoallergenic derivatives thereof could provide a convenient and safe intervention strategy against type I allergy.

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Section: Methodsmentioning

confidence: 99%

Intranasal Treatment with a Recombinant Hypoallergenic Derivative of the Major Birch Pollen Allergen Bet v 1 Prevents Allergic Sensitization and Airway Inflammation in Mice

Wiedermann¹,

Herz

Baier³

et al. 2001

Int Arch Allergy Immunol

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“…OVA-specific IgE, IgG1, and IgG2a concentrations were determined by ELISA technique as described previously (23).…”

Section: Measurements Of Ova-specific Ig Titers In Serum Samplesmentioning

confidence: 99%

Immunomodulatory Effects of Viral TLR Ligands on Experimental Asthma Depend on the Additive Effects of IL-12 and IL-10

Wegmann

Sel

Bauer

et al. 2007

The Journal of Immunology

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107

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Based on epidemiological data, the hygiene hypothesis associates poor hygienic living conditions during childhood with a lower risk for the development of allergic diseases such as bronchial asthma. The role of viral infections, and especially of viral TLR ligands, within this context remains to be clarified. Viral TLR ligands involve dsRNA and ssRNA which are recognized by TLR-3 or TLR-7, respectively. In this study, we evaluated the impact of TLR-3 or TLR-7 activation on experimental asthma in mice. Systemic application of the synthetic TLR-3 or TLR-7 ligands polycytidylic-polyinosinic acid (p(I:C)) or R-848, respectively, during the sensitization phase prevented the production of OVA-specific IgE and IgG1 Abs and subsequently abolished all features of experimental asthma including airway hyperresponsiveness and allergic airway inflammation. Furthermore, administration of p(I:C) or R-848 to animals with already established primary allergic responses revealed a markedly reduced secondary response following allergen aerosol rechallenges. In contrast to wild-type animals, application of p(I:C) or R-848 to IL-12p35−/− mice had no effect on airway inflammation, goblet cell hyperplasia, and airway hyperresponsiveness. However, in the absence of IL-12, the numbers of eosinophils and lymphocytes in bronchoalveolar lavage fluids were still significantly reduced. These partial effects could also be abolished by neutralizing anti-IL-10 Abs in IL-12p35−/− mice. These data indicate that TLR-3 or TLR-7 activation by viral TLR ligands has both preventive as well as suppressive effects on experimental asthma which is mediated by the additive effects of IL-12 and IL-10.

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“…Measurements of airway responsiveness were performed 24 h after the last challenge (day 28) by head-out body plethysmography, as previously described (23). Air flow signals were recorded in response to methacholine (0, 12.5, 25, 50, 100, 200 mg/ml) and aerosolized with a nebulizer.…”

Section: Determination Of Airway Responsivenessmentioning

confidence: 99%

α-Melanocyte-Stimulating Hormone Inhibits Allergic Airway Inflammation

Raap

Brzoska²,

Sohl

et al. 2003

The Journal of Immunology

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α-Melanocyte-stimulating hormone (α-MSH) is a neuropeptide controlling melanogenesis in pigmentary cells. In addition, its potent immunomodulatory and immunosuppressive activity has been recently described in cutaneous inflammatory disorders. Whether α-MSH is also produced in the lung and might play a role in the pathogenesis of inflammatory lung conditions, including allergic bronchial asthma, is unknown. Production and functional role of α-MSH were investigated in a murine model of allergic airway inflammation. α-MSH production was detected in bronchoalveolar lavage fluids. Although aerosol challenges stimulate α-MSH production in nonsensitized mice, this rapid and marked stimulation was absent in allergic animals. Treatment of allergic mice with α-MSH resulted in suppression of airway inflammation. These effects were mediated via IL-10 production, because IL-10 knockout mice were resistant to α-MSH treatment. This study provides evidence for a novel function of α-MSH linking neuroimmune functions in allergic airway inflammation.

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

Cited by 78 publications

References 26 publications

Intranasal Treatment with a Recombinant Hypoallergenic Derivative of the Major Birch Pollen Allergen Bet v 1 Prevents Allergic Sensitization and Airway Inflammation in Mice

Intranasal Treatment with a Recombinant Hypoallergenic Derivative of the Major Birch Pollen Allergen Bet v 1 Prevents Allergic Sensitization and Airway Inflammation in Mice

Immunomodulatory Effects of Viral TLR Ligands on Experimental Asthma Depend on the Additive Effects of IL-12 and IL-10

α-Melanocyte-Stimulating Hormone Inhibits Allergic Airway Inflammation

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