Establishment and characterization of murine models of asthma and subcutaneous immunotherapy for Humulus pollen allergy

Abstract

Introduction Humulus pollen is an important cause of allergic asthma in East Asia. There have been some murine models for Humulus pollen allergy established by intraperitoneal (IP) sensitization and nasal drip stimulation, but they were not comprehensive enough. Here, we used atomized inhalation for challenge and compared the subcutaneous (SC) and IP sensitization routes to determine the optimal method to establish a model of asthma induced by Humulus pollen. Subsequently, we tried to develop a rapid subcutaneous immunotherapy (SCIT) model for Humulus allergy. Methods BALB/c Mice were sensitized through the SC or IP route, with respective reference to previously established sensitization methods and allergen dosing, and challenged with nebulized Humulus pollen extract to induce asthma. To compare the two sensitization methods, airway hyperresponsiveness (AHR), inflammatory cell infiltration, allergen‐specific serum immunoglobulin (Ig)E (sIgE) levels, cytokine levels, and lung histopathology were assessed. The effects of SCIT (once every other day for 16 days) on airway inflammation, AHR, sIgE, and allergen‐specific serum IgG2a (sIgG2a) levels were evaluated by using the model established in this study. Results Although mice sensitized by the SC or IP routes both showed AHR and airway inflammation, the SC route elicited significantly higher levels of sIgE, eosinophil inflammation, and T helper type 2 cytokines, compared with the IP route. SCIT in the treatment group significantly reduced the titers of sIgE, enhanced the titers of sIgG2a, and effectively alleviated pulmonary inflammation and AHR, compared with the vehicle group. Conclusions The SC route can be used to establish a murine model of Humulus pollen allergy that recapitulates the characteristics of clinical allergic asthma. Short‐term SCIT can significantly improve symptoms and pathophysiology in asthmatic mice.

(1→3)-β-D-glucan derivatives with unique structural properties differentially affect murine lung inflammation and histology

“…1-5, 8 . The neutrophil and lymphocyte migration into the airspace observed in lung micrographs were reminiscent of a murine asthma model (46), however, our cytokine data supports a mixed Th1/17 immune response to BDGs, Fig. 3 .…”

Exposure to structurally unique β‐d‐glucans differentially affects inflammatory responses in male mouse lungs

“…Pustulan increased total BAL protein concentration, immune cell infiltrate, and cytokine concentrations, IgE and IgG2a, compared to control Figures 1-4, 6. The neutrophil and lymphocyte migration into the airspace observed in lung micrographs was reminiscent of a murine asthma model (Xi et al, 2021); however, our cytokine data supports a mixed Th1/17 immune response to BDGs (Figure 3). Gene-environment interactions likely lead to distinct mold-induced phenotypes (Barnes, 1999).…”