Abstract
The effects of different sensitization and allergen provocation regimens on the development of allergen-induced bronchial hyperreactivity (BHR) to histamine were investigated in conscious, unrestrained guinea-pigs. Similar early and late phase asthmatic reactions, BHR for inhaled histamine after the early (6 h) as well as after the late reaction (24 h), and airway inflammation were observed after a single allergen provocation in animals sensitized to produce mainly IgG or IgE antibodies, respectively. Repeating the allergen provocation in the IgE-sensitized animals after 7 days, using identical provocation conditions, resulted in a similar development of BHR to histamine inhalation. Repetition of the allergen provocation during 4 subsequent days resulted in a decreased development of BHR after each provocation, despite a significant increase in the allergen provocation dose necessary to obtain similar airway obstruction. The number of inflammatory cells in the bronchoalveolar lavage was not significantly changed after repeated provocation, when compared with a single allergen provocation. Finally, we investigated allergen-induced bronchial hyperreactivity by repetition of the sensitization procedure at day 7 and 14 (booster), followed by repeated allergen provocation twice a week for 5 weeks. Surprisingly, no BHR to histamine could be observed after either provocation, while the number of inflammatory cells in the bronchoalveolar lavage fluid after 5 weeks was enhanced compared with controls. These data indicate that both IgE and IgG sensitized guinea-pigs may develop bronchial hyperreactivity after a single allergen provocation. Repeated allergen exposure of IgE sensitized animals causes a gradual fading of the induced hyperreactivity despite the on-going presence of inflammatory cells in the airways, indicating a mechanism of reduced cellular activation.
Highlights
Allergen-induced early (EAR) and late (LAR) phase asthmatic reactions, bronchial hyperreactivity (BHR), and airway inflammation are common characteristics of allergic asthma
Influence ofthe sensitization regimen: In the first part of this study the development of early and late phase asthmatic reactions, bronchial hyperreactivity and airway inflammation induced by a single allergen provocation was investigated in guinea-pigs sensitized to produce predominantly IgG or IgE antibodies
Addition of FCA resulted in production of almost exclusively (99%) IgG antibodies, whereas in animals treated with AI(OH) 44% of the antibodies were of the IgE class
Summary
Allergen-induced early (EAR) and late (LAR) phase asthmatic reactions, bronchial hyperreactivity (BHR), and airway inflammation are common characteristics of allergic asthma. 1-3 It was observed that bronchial reactivity was already increased before the LAR was clinically manifest, suggesting that this early developed BHR may contribute to the severity of the LAR. The development of the LAR and the allergen-induced increase in bronchial reactivity are associated with an influx of inflammatory cells into the airways,[4,5] indicating that. Cutaneous late phase reactions are IgE-dependent and can be transferred passively; the ability to perform these passive transfers is eliminated by removal of the IgE antibodies from the serum and restored by administration of the IgE fraction.[6,7] Evidence that LARs are IgE-dependent comes from the observation that they can be produced by inhalation of anti-IgE antibodies
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