Abstract:Despite improvements in anti-allergy medication, the prevalence of allergic airway inflammation remains high, affecting up to 40% of the population worldwide. Allergen immunotherapy is effective for inducing tolerance but has the adverse effect of severe allergic reaction. This can be avoided by denaturing with urea. In this study, we demonstrated that the serum level of allergen-specific IgE in mice sensitized with native Dermatophagoides pteronyssinus (Der p) crude extract after receiving local nasal immunot… Show more
“… 171 , 172 These result in a reduction in inflammation in the affected tissue, as shown both in double-blinded patient studies and animal models. 173 , 174 Finally, AIT has also been shown to prevent ILC2 increase during pollen seasons in patients with AR 175 by as yet unknown mechanisms. Fig.…”
Allergic diseases are highly prevalent worldwide and affect all age groups, contributing to a high personal and socioeconomic burden. Treatment with an “allergy vaccine” or allergen immunotherapy aims to provide long-lasting benefits by inducing unresponsiveness to the relevant antigen. The consequences of the therapy are considered disease modifying and range from dampening of the immediate immune responses to the reduction of secondary tissue remodeling. Furthermore, allergen immunotherapy interventions have a potential to slow or cease the development of additional allergic manifestations with a long-term overall effect on morbidity and quality of life. Here, we review proposed mechanisms underlying the therapeutic effects of immunotherapy for allergic diseases. Further, we discuss both standard and novel approaches and possible future directions in the development of allergen immunotherapy.
“… 171 , 172 These result in a reduction in inflammation in the affected tissue, as shown both in double-blinded patient studies and animal models. 173 , 174 Finally, AIT has also been shown to prevent ILC2 increase during pollen seasons in patients with AR 175 by as yet unknown mechanisms. Fig.…”
Allergic diseases are highly prevalent worldwide and affect all age groups, contributing to a high personal and socioeconomic burden. Treatment with an “allergy vaccine” or allergen immunotherapy aims to provide long-lasting benefits by inducing unresponsiveness to the relevant antigen. The consequences of the therapy are considered disease modifying and range from dampening of the immediate immune responses to the reduction of secondary tissue remodeling. Furthermore, allergen immunotherapy interventions have a potential to slow or cease the development of additional allergic manifestations with a long-term overall effect on morbidity and quality of life. Here, we review proposed mechanisms underlying the therapeutic effects of immunotherapy for allergic diseases. Further, we discuss both standard and novel approaches and possible future directions in the development of allergen immunotherapy.
“…The Der p 2-induced allergic airway inflammation has been established in our previous study that the leukocyte subpopulation (neutrophils and eosinophils) in BAL, specific immunoglobulin (IgE), inflammatory cytokine (IL-5), pulmonary function, and lung pathology significantly changed in the Der p 2-sensitized and challenged mice [ 13 ]. The HDM-induced asthma animal model has been reported to be useful for the evaluation of the effectiveness of immunotherapy [ 14 ]. Intraperitoneal sensitization followed by intratracheal challenge with mite extract can induce airway inflammation, tracheal rupture, and tracheal thickening in the asthmatic mouse model [ 15 ]; therefore, this asthmatic model is suitable to evaluate the therapeutic effectiveness of candidate medicine like Traditional Chinese Medicine (TCM) on mite-induced allergic responses [ 15 ].…”
Background
Allergic asthma occurs worldwide and is particularly prevalent in westernized countries characterized by chronic airway inflammation resulting in airway hyperresponsiveness. The house dust mites (HDM) including Dermatophagoides pteronyssinus are major sources of sensitization and triggering allergic symptoms in asthmatic patients. The Der p 2 is a major allergen and the predominant source of causative respiratory disorders which induce airway inflammation and bronchial constriction in mite-allergic patients. Few studies evaluate the ameliorating effects of modified Liu-Wei-Di-Huang-Wan (modified LWDHW) on allergic asthma.
Methods
This study aimed to investigate the immunological mechanisms of modified LWDHW on the reductions of airway inflammation, signal transduction, inflammatory cytokine production, Th2 cell proliferation, and bronchial obstruction in Der p 2-induced asthmatic mice.
Results
At least ten active ingredients were contained in the formula of modified LWDHW- 1217A and 1217B. Results showed that the immunoglobulin generations (Der p 2 specific- IgE and IgG1), inflammatory cytokine productions (IL-5 and IL-13) in the Sera and BALF could be down-regulated, and the Th1-cytokine productions (IL-12 and IFN-γ) be increased after immunotherapy with modified LWDHW of 1217A or 1217B. The inflammatory cell infiltrations (macrophages, eosinophils, and neutrophils) in the airway and the expressions of TH2-related genes (IL-4, IL-5, and IL-13), TH2-related transcription factor (GATA-3), and neutrophil chemotactic chemokine (IL-8) in the lung tissue of asthmatic mice were significantly decreased after the immunotherapy. The Th1/Th2 polarization had been identified that the IL-4+/CD4+ T cells were downregulated and IFN-γ+/CD4+ T cells were increased. The airway hyperresponsiveness to methacholine inhalation of Penh values was significantly decreased in the treated groups. There were significant improvements in the bronchus histopathology after immunotherapy with 1217A or 1217B which were evaluated by tracheal thickness, inflammatory cell count, and tracheal rupture of mouse lung.
Conclusion
It revealed that 1217A or 1217B could regulate the immune responses and improve pulmonary function. Data suggests that modified LWDHW of 1217A or 1217B have the potential for use as a therapeutic intervention for the treatment of mite allergen Der p 2-induced allergic asthma.
“…The Der p 2-induced allergic airway in ammation has been established in our previous study that the leukocyte subpopulation (neutrophils and eosinophils) in BAL, speci c immunoglobulin (IgE), in ammatory cytokine (IL-5), pulmonary function, and lung pathology signi cantly changed in the Der p 2-sensitized and challenged mice 13 . The HDMinduced asthma animal model has been reported to be useful for the evaluation of the effectiveness of immunotherapy 14 . Intraperitoneal sensitization followed by intratracheal challenge with mite extract can induce airway in ammation, tracheal rupture, and tracheal thickening in the asthmatic mouse model 15 ; therefore, this asthmatic model is suitable to evaluate the therapeutic effectiveness of candidate medicine like Traditional Chinese Medicine (TCM) on mite-induced allergic responses 15 .…”
Background
Allergic asthma occurs worldwide and is particularly prevalent in westernized countries characterized by chronic airway inflammation resulting in airway hyperresponsiveness. The house dust mites (HDM) including Dermatophagoides pteronyssinus are major sources of sensitization and triggering allergic symptoms in asthmatic patients. The Der p 2 is a major allergen and the predominant source of causative respiratory disorders which induce airway inflammation and bronchial constriction in mite-allergic patients. Few studies evaluate the ameliorating effects of modified Liu-Wei-Di-Huang-Wan (modified LWDHW) on allergic asthma.
Methods
This study aimed to investigate the immunological mechanisms of modified LWDHW on the inhibitory effects of airway inflammation, signal transduction, inflammatory cytokine production, Th2 cell proliferation, and bronchial obstruction in Der p 2-induced asthmatic mice.
Results
At least ten active ingredients were contained in the formula of modified LWDHW- 1217A and 1217B. Results showed that the immunoglobulin generations (Der p 2 specific- IgE and IgG1), inflammatory cytokine productions (IL-5 and IL-13) in the Sera and BALF could be down-regulated, and the Th1-cytokine productions (IL-12 and IFN-γ) be increased after immunotherapy with modified LWDHW of 1217A or 1217B. The inflammatory cell infiltrations (macrophages, eosinophils, and neutrophils) in the airway and the expressions of TH2-related genes (IL4, IL5, and IL13), TH2-related transcription factor (GATA-3), and neutrophil chemotactic chemokine (IL8) in the lung tissue of asthmatic mice were significantly decreased after the immunotherapy. The Th1/Th2 polarization had been identified that the IL-4+/CD4+ T cells were downregulated and IFN-γ+/CD4+ T cells were increased. The airway hyperresponsiveness to methacholine inhalation of Penh values was significantly decreased in the treated groups. There were significant improvements in the bronchus histopathology after immunotherapy with 1217A or 1217B which were evaluated by tracheal thickness, inflammatory cell count, and tracheal rupture of mouse lung.
Conclusions
It revealed that 1217A or 1217B could regulate the immune responses and improve pulmonary function. Data suggests that modified LWDHW of 1217A or 1217B have the potential for use as a therapeutic modality for the treatment of mite allergen Der p 2-induced allergic asthma.
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