Mycobacterium vaccae administration during allergen sensitization or challenge suppresses asthmatic features.
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 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 On day 43, the airway responsiveness of the mice to increasing concentrations of methacholine was assessed, blood was withdrawn to measure serum parameters, and lung lavage was performed to detect cytokines and inflammatory cell number.


RESULTS
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.


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.
Smit
J J
JJ
Department of Pharmacology and Pathophysiology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands.
Van Loveren
H
H
Hoekstra
M O
MO
Schijf
M A
MA
Folkerts
G
G
Nijkamp
F P
FP
D000485:Allergens / Q000276:immunology*; D000818:Animals; D001249:Asthma / Q000276:immunology / Q000517:prevention & control / Q000628:therapy*; D001428:Bacterial Vaccines / Q000627:therapeutic use*; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016085:Bronchoconstrictor Agents; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D007136:Immunoglobulins / Q000096:biosynthesis; D007958:Leukocyte Count; D008297:Male; D016210:Methacholine Chloride; D051379:Mice; D008807:Mice, Inbred BALB C; D009161:Mycobacterium / Q000276:immunology; D010047:Ovalbumin / Q000276:immunology; D011657:Pulmonary Eosinophilia / Q000628:therapy
D000485:Allergens; D001428:Bacterial Vaccines; D016085:Bronchoconstrictor Agents; D016207:Cytokines; D007136:Immunoglobulins; D016210:Methacholine Chloride; C451081:SRL172; D010047:Ovalbumin