在哮喘模型中，简化中药干预治疗哮喘诱导的对过敏原的长期耐受，与γ干扰素而非转化生长因子β有关
2010/09/14
摘要
背景：慢性过敏性哮喘可能是免疫状态向2型T辅助细胞（Th2）偏移的结果。目前，一些哮喘患者所接受的治疗主要以控制症状为主，尚未建立长期治疗方法。抗哮喘简化中药干预治疗(ASHMI)项目，旨在持续性中度至重度哮喘患者中，采用中药制剂改善症状和肺功能、减少Th2反应。
目的：本文旨在小鼠慢性哮喘模型中评价ASHMI 治疗作用的持续性及其治疗作用的免疫学机制。
方法：通过腹腔注射卵清蛋白（OVA）对BALB/c小鼠致敏，这些小鼠采用3次气管内OVA激发，诱导气道高反应性（AHR）和炎症（OVA小鼠）。此外，OVA小鼠采用ASHMI（OVA/ASHMI组）或生理盐水（OVA/sham组）连续治疗4周，治疗后即刻和治疗后8周进行激发试验。在其他实验中，OVA小鼠除给予ASHMI 治疗外，同时给予IFN-γ或TGF-β中和抗体治疗。治疗后8周，检测气道反应性、细胞因子和OVA特异性IgE水平。
结果：治疗前，OVA小鼠在OVA激发后表现为AHR和肺嗜酸性粒细胞炎症，在ASHMI治疗后上述表现完全、即刻缓解，而且上述表现即使在治疗8周后OVA激发时也不会再次出现。过敏原特异性IgE和Th2细胞因子水平降低及IFN-γ水平增加能持续到治疗后8周。给予IFN-γ，而非TGF-β中和抗体治疗后，ASHMI的治疗作用消失。
结论：ASHMI治疗能产生对过敏原诱导的炎症和AHR长期耐受，该作用与IFN-γ有关。
（苏楠 审校）
Clin Exp Allergy. 2010 Jun 22. [Epub ahead of print]
Anti-Asthma Simplified Herbal Medicine Intervention-induced long-lasting tolerance to allergen exposure in an asthma model is interferon-gamma, but not transforming growth factor-beta dependent
Srivastava K, Zhang T, Yang N, Sampson H, Li XM.
Department of Pediatrics, Division of Allergy & Immunology, The Mount Sinai School of Medicine, New York, NY, USA.
Abstract
Background Chronic allergic asthma is the result of a T-helper type 2 (Th2)-biased immune status. Current asthma therapies control symptoms in some patients, but a long-lasting therapy has not been established. Anti-Asthma Simplified Herbal Medicine Intervention (ASHMI), a Chinese herbal formula improved symptoms and lung function, and reduced Th2 responses in a controlled trial of patients with persistent moderate to severe asthma. Objective We evaluated the persistence of ASHMI() beneficial effects following therapy in a murine model of chronic asthma and the immunological mechanisms underlying such effects. Methods BALB/c mice sensitized intraperitoneally with ovalbumin (OVA) received 3 weekly intratracheal OVA challenges to induce airway hyper-reactivity (AHR) and inflammation (OVA mice). Additionally, OVA mice were treated with ASHMI() (OVA/ASHMI()) or water (OVA/sham) for 4 weeks, and then challenged immediately and 8 weeks post-therapy. In other experiments, OVA mice received ASHMI() treatment with concomitant neutralization of IFN-gamma or TGF-beta. Effects on airway responses, cytokine- and OVA-specific IgE levels were determined 8 weeks post-therapy. Results Before treatment, OVA mice exhibited AHR and pulmonary eosinophilic inflammation following OVA challenge, which was almost completely resolved immediately after completing treatment with ASHMI() and did not re-occur following OVA re-challenge up to 8 weeks post-therapy. Decreased allergen-specific IgE and Th2 cytokine levels, and increased IFN-gamma levels also persisted at least 8 weeks post-therapy. ASHMI() effects were eliminated by the neutralization of IFN-gamma, but not TGF-beta, during therapy. Conclusion ASHMI() induced long-lasting post-therapy tolerance to antigen-induced inflammation and AHR. IFN-gamma is a critical factor in ASHMI() effects.
Clin Exp Allergy. 2010 Jun 22. [Epub ahead of print]
背景：慢性过敏性哮喘可能是免疫状态向2型T辅助细胞（Th2）偏移的结果。目前，一些哮喘患者所接受的治疗主要以控制症状为主，尚未建立长期治疗方法。抗哮喘简化中药干预治疗(ASHMI)项目，旨在持续性中度至重度哮喘患者中，采用中药制剂改善症状和肺功能、减少Th2反应。
目的：本文旨在小鼠慢性哮喘模型中评价ASHMI 治疗作用的持续性及其治疗作用的免疫学机制。
方法：通过腹腔注射卵清蛋白（OVA）对BALB/c小鼠致敏，这些小鼠采用3次气管内OVA激发，诱导气道高反应性（AHR）和炎症（OVA小鼠）。此外，OVA小鼠采用ASHMI（OVA/ASHMI组）或生理盐水（OVA/sham组）连续治疗4周，治疗后即刻和治疗后8周进行激发试验。在其他实验中，OVA小鼠除给予ASHMI 治疗外，同时给予IFN-γ或TGF-β中和抗体治疗。治疗后8周，检测气道反应性、细胞因子和OVA特异性IgE水平。
结果：治疗前，OVA小鼠在OVA激发后表现为AHR和肺嗜酸性粒细胞炎症，在ASHMI治疗后上述表现完全、即刻缓解，而且上述表现即使在治疗8周后OVA激发时也不会再次出现。过敏原特异性IgE和Th2细胞因子水平降低及IFN-γ水平增加能持续到治疗后8周。给予IFN-γ，而非TGF-β中和抗体治疗后，ASHMI的治疗作用消失。
结论：ASHMI治疗能产生对过敏原诱导的炎症和AHR长期耐受，该作用与IFN-γ有关。
（苏楠 审校）
Clin Exp Allergy. 2010 Jun 22. [Epub ahead of print]
Anti-Asthma Simplified Herbal Medicine Intervention-induced long-lasting tolerance to allergen exposure in an asthma model is interferon-gamma, but not transforming growth factor-beta dependent
Srivastava K, Zhang T, Yang N, Sampson H, Li XM.
Department of Pediatrics, Division of Allergy & Immunology, The Mount Sinai School of Medicine, New York, NY, USA.
Abstract
Background Chronic allergic asthma is the result of a T-helper type 2 (Th2)-biased immune status. Current asthma therapies control symptoms in some patients, but a long-lasting therapy has not been established. Anti-Asthma Simplified Herbal Medicine Intervention (ASHMI), a Chinese herbal formula improved symptoms and lung function, and reduced Th2 responses in a controlled trial of patients with persistent moderate to severe asthma. Objective We evaluated the persistence of ASHMI() beneficial effects following therapy in a murine model of chronic asthma and the immunological mechanisms underlying such effects. Methods BALB/c mice sensitized intraperitoneally with ovalbumin (OVA) received 3 weekly intratracheal OVA challenges to induce airway hyper-reactivity (AHR) and inflammation (OVA mice). Additionally, OVA mice were treated with ASHMI() (OVA/ASHMI()) or water (OVA/sham) for 4 weeks, and then challenged immediately and 8 weeks post-therapy. In other experiments, OVA mice received ASHMI() treatment with concomitant neutralization of IFN-gamma or TGF-beta. Effects on airway responses, cytokine- and OVA-specific IgE levels were determined 8 weeks post-therapy. Results Before treatment, OVA mice exhibited AHR and pulmonary eosinophilic inflammation following OVA challenge, which was almost completely resolved immediately after completing treatment with ASHMI() and did not re-occur following OVA re-challenge up to 8 weeks post-therapy. Decreased allergen-specific IgE and Th2 cytokine levels, and increased IFN-gamma levels also persisted at least 8 weeks post-therapy. ASHMI() effects were eliminated by the neutralization of IFN-gamma, but not TGF-beta, during therapy. Conclusion ASHMI() induced long-lasting post-therapy tolerance to antigen-induced inflammation and AHR. IFN-gamma is a critical factor in ASHMI() effects.
Clin Exp Allergy. 2010 Jun 22. [Epub ahead of print]
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支气管哮喘患儿低剂量红霉素治疗的指征和有效性
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中年哮喘患者对哮喘治疗指南的依从性分析
