Department of Respiratory Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People's Republic of China.
J Aerosol Med Pulm Drug Deliv. 2012 Apr;25(2):96-103. doi: 10.1089/jamp.2011.0904. Epub 2011 Dec 8.
Corticosteroids are the most efficacious anti-inflammatory drugs for asthma therapy; however, steroids are not always completedly effective for asthma. Studies have shown Mycobacterium bovis Bacille Calmette-Guérin (BCG) and other mycobacterial infections suppress airway hyperresponsiveness and inflammation in asthma. We use a murine model of Ovalbumin (OVA)-induced asthma to study whether nebulized inhalation of inactivated Mycobacterium phlei can alleviate asthmatic airway inflammation through influencing cytokine production and determine whether it can prevent and treat asthma.
Fifth male Balb/c mice were randomly divided into four groups: normal control group (A), asthma model group (B0, B3, B4, B5), the treatment group (C0, C3, C4, C5), and prevention group (D). Mice were sensitizated and challenged with Ovalbumin to make a murine asthma model. Group C were given treatment of aerosol Mycobacterium phlei once daily after OVA challenge. Groups C3, C4, and C5 were treated for 3 days, 4 days, and 5 days, respectively. Group D inhaled the solution of inactivated Mycobacterium phlei daily before each time of OVA challenge. All the animals were killed and lung tissue and bronchoalveolar lavage fluid (BALF) were harvested. Pathological HE staining and AB-PAS staining were done to measure lung inflammation and mucus production. Total cell numbers and differential cell count in BALF were performed. Cytokines IL-4, IL-10, and IFN-γ levels in BALF were quantified by ELISA.
In groups C4, C5, and D, IL-4 production in BALF was decreased and IL-10 and IFN-γ were increased (p<0.05).The number of total inflammatory cells and the mean percentage of eosinophils and lymphocytes in the BALF of group D, group C4, and group C5 was lower than in the corresponding group B (p<0.05). Histological examination of the lungs showed airway inflammation of group D and group C5 were attenuated.
The inhalation of Mycobacterium phlei can reduce airway inflammation in asthmatic mice. This ability was associated with its immunomodulatory effect on regulating IL-4, IL-10, and IFN-γ secretion. Aerosol administration of inactivated Mycobacterium phlei may be accepted as an alternative method with less risk of adverse reactions in treatment of asthma.
皮质类固醇是治疗哮喘最有效的抗炎药物;然而,类固醇并不总是完全有效治疗哮喘。研究表明,牛分枝杆菌和其他分枝杆菌感染可以抑制哮喘的气道高反应性和炎症。我们使用卵清蛋白(OVA)诱导的哮喘小鼠模型来研究雾化吸入灭活草分枝杆菌是否可以通过影响细胞因子的产生来减轻哮喘气道炎症,并确定其是否可以预防和治疗哮喘。
第五只雄性 Balb/c 小鼠被随机分为四组:正常对照组(A)、哮喘模型组(B0、B3、B4、B5)、治疗组(C0、C3、C4、C5)和预防组(D)。用卵清蛋白致敏和激发小鼠制作哮喘模型。在 OVA 激发后,C 组每天给予雾化草分枝杆菌治疗。C3、C4 和 C5 组分别治疗 3 天、4 天和 5 天。D 组在每次 OVA 激发前每天吸入灭活草分枝杆菌溶液。处死所有动物,采集肺组织和支气管肺泡灌洗液(BALF)。进行病理 HE 染色和 AB-PAS 染色以测量肺炎症和粘液产生。对 BALF 中的总细胞数和分类细胞计数进行分析。通过 ELISA 定量 BALF 中细胞因子 IL-4、IL-10 和 IFN-γ 的水平。
在 C4、C5 和 D 组中,BALF 中 IL-4 的产生减少,IL-10 和 IFN-γ 增加(p<0.05)。D 组、C4 组和 C5 组 BALF 中的总炎性细胞数和嗜酸性粒细胞和淋巴细胞的平均百分比均低于相应的 B 组(p<0.05)。肺部组织学检查显示 D 组和 C5 组的气道炎症减轻。
雾化吸入草分枝杆菌可以减轻哮喘小鼠的气道炎症。这种能力与其对调节 IL-4、IL-10 和 IFN-γ 分泌的免疫调节作用有关。雾化给予灭活草分枝杆菌可能被接受为一种替代方法,其在治疗哮喘方面的不良反应风险较低。