Smit J J, Van Loveren H, Hoekstra M O, Schijf M A, Folkerts G, Nijkamp F P
Department of Pharmacology and Pathophysiology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands.
Clin Exp Allergy. 2003 Aug;33(8):1083-9. doi: 10.1046/j.1365-2222.2003.01727.x.
The hygiene hypothesis suggests that a lack of bacterial infections would favour the development of allergic disease. For this reason, bacteria or their components can be used as potential treatment for allergic asthma. We investigated whether heat-killed Mycobacterium vaccae is either able to suppress the induction of allergic asthma or able to suppress already established allergic asthma.
Mice were sensitized with ovalbumin (OVA)/alum on days 0 and 14. Thereafter, mice were challenged on days 35, 39 and 42 by inhalation of either OVA or saline aerosols. M. vaccae-treated mice received an injection with 106, 107 or 108 CFU heat-killed M. vaccae on days 0 and 14 or 107 CFU on days 35 and 39. On day 43, the airway responsiveness of the mice to increasing concentrations of methacholine was assessed, blood was withdrawn to measure serum parameters, and lung lavage was performed to detect cytokines and inflammatory cell number.
Treatment of OVA-sensitized mice with 107 CFU M. vaccae either during sensitization or challenge suppresses airway hyper-responsiveness, airway eosinophilia and IL-5 production after OVA challenge. The increases in OVA-specific serum IgE and in IL-4 by respiratory challenges with OVA were only diminished after M. vaccae treatment (107 CFU) during sensitization.
Heat-killed M. vaccae prevents allergic and asthmatic manifestations in a mouse model and, more importantly, M. vaccae treatment during challenge suppresses features of asthma, which opens up possibilities for new therapeutic interventions.
卫生假说表明缺乏细菌感染会促进过敏性疾病的发展。因此,细菌或其成分可作为过敏性哮喘的潜在治疗方法。我们研究了热灭活的母牛分枝杆菌是否能够抑制过敏性哮喘的诱导或抑制已建立的过敏性哮喘。
在第0天和第14天用卵清蛋白(OVA)/明矾对小鼠进行致敏。此后,在第35、39和42天通过吸入OVA或盐雾对小鼠进行激发。经母牛分枝杆菌处理的小鼠在第0天和第14天接受10⁶、10⁷或10⁸CFU热灭活的母牛分枝杆菌注射,或在第35天和第39天接受10⁷CFU注射。在第43天,评估小鼠对递增浓度乙酰甲胆碱的气道反应性,采集血液测量血清参数,并进行肺灌洗以检测细胞因子和炎症细胞数量。
在致敏或激发期间用10⁷CFU母牛分枝杆菌处理OVA致敏的小鼠,可抑制OVA激发后的气道高反应性、气道嗜酸性粒细胞增多和IL - 5产生。仅在致敏期间用母牛分枝杆菌处理(10⁷CFU)后,OVA激发引起的OVA特异性血清IgE和IL - 4增加才有所减少。
热灭活的母牛分枝杆菌可预防小鼠模型中的过敏性和哮喘表现,更重要的是,在激发期间进行母牛分枝杆菌处理可抑制哮喘特征,这为新的治疗干预开辟了可能性。