title: Mycobacterial antigens attenuate late phase response, airway hyperresponsiveness, and bronchoalveolar lavage eosinophilia in a mouse model of bronchial asthma.
abstract: Allergens, in combination with genetic predisposition, drive undifferentiated T cells towards the type 2 T cells. Some childhood infections may activate the production of a type 1 T cell profile. It is reasonable to speculate that a decrease in childhood infections may increase the incidence of allergy by allowing the immune balance to shift towards the type 2 T cells. We hypothesized that pre-exposure of mycobacterial antigens in sensitized mice would prevent the development of asthma-like conditions. Specifically, we examined the effect of mycobacterial antigens, Bacillus Calmette-Guerin (BCG) vaccine and Mycobacterium vaccae, on antigen-induced bronchoconstriction, airway hyperresponsiveness to methacholine, bronchoalveolar lavage eosinophilia, and plasma IL-4 and IL-12 levels in ovalbumin (OVA)-sensitized and challenged Balb/c mice. Challenge with OVA produced a 2-3-fold increase in bronchoconstriction within 3-5 min, followed by a delayed response after 60 min, the latter of which was significantly attenuated by both BCG and M. vaccae. Airway hyperresponsiveness to methacholine 24 h after OVA challenge was prevented by BCG and M. vaccae. Airway eosinophilia was also prevented by BCG and M. vaccae. The plasma IL-12 levels were significantly increased and plasma IL-4 levels were significantly decreased following BCG or M. vaccae administration in OVA-sensitized and challenged mice. Interestingly, a significant increase in plasma IL-12 was observed with BCG as compared to M. vaccae administration, suggesting a stronger type 1 response to BCG. These data support our hypothesis and suggest that BCG and M. vaccae may prevent the underlying pathophysiological changes in asthma.
authors.affiliation: Center for Allergy, Asthma and Immunology, Creighton University School of Medicine, Omaha, NE 68178, USA.
authors.forename: M T
authors.initials: MT
authors.lastname: Hopfenspirger
authors.forename: S K
authors.initials: SK
authors.lastname: Parr
authors.forename: R J
authors.initials: RJ
authors.lastname: Hopp
authors.forename: R G
authors.initials: RG
authors.lastname: Townley
authors.forename: D K
authors.initials: DK
authors.lastname: Agrawal
mesh_terms: D000465:Algorithms; D000818:Animals; D000942:Antigens, Bacterial / Q000494:pharmacology*; D001249:Asthma / Q000473:pathology*; D016535:Bronchial Hyperreactivity / Q000503:physiopathology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology*; D016207:Cytokines / Q000378:metabolism; D004802:Eosinophilia / Q000473:pathology*; D018664:Interleukin-12 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D016210:Methacholine Chloride / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D018721:Muscarinic Agonists / Q000494:pharmacology; D009161:Mycobacterium / Q000276:immunology*; D009163:Mycobacterium bovis / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D016207:Cytokines; D018721:Muscarinic Agonists; D016210:Methacholine Chloride; D018664:Interleukin-12; D015847:Interleukin-4