Mycobacterium vaccae administration during allergen sensitization or challenge suppresses asthmatic features

被引:32
作者
Smit, JJ
Van Loveren, H
Hoekstra, MO
Schijf, MA
Folkerts, G
Nijkamp, FP
机构
[1] Univ Utrecht, Utrecht Inst Pharmaceut Sci, Dept Pharmacol & Pathophysiol, NL-3508 TB Utrecht, Netherlands
[2] Natl Inst Publ Hlth & Environm, Lab Pathol & Immunobiol, Bilthoven, Netherlands
[3] Wilhelmina Childrens Hosp, UMC, Dept Gen Pediat, Utrecht, Netherlands
关键词
airway hyper-responsiveness; allergy; asthma; eosinophilia; lung; Mycobacterium vaccae; Th1; Th2; cells;
D O I
10.1046/j.1365-2222.2003.01727.x
中图分类号
R392 [医学免疫学];
学科分类号
100102 ;
摘要
Background and objective 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. Methods 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 10(6), 10(7) or 10(8) CFU heat-killed M. vaccae on days 0 and 14 or 10(7) 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 On day 43, the airway responsiveness of the mice to increasing concentrations of methacholine was assessed, blood was withdrawn to measure serum parameters, and lung lavage was performed to detect cytokines and inflammatory cell number. Results Treatment of OVA-sensitized mice with 10(7) 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 (10(7) CFU) during sensitization. Conclusions 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.
引用
收藏
页码:1083 / 1089
页数:7
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