Mycobacterial antigens attenuate late phase response, airway hyperresponsiveness, and bronchoalveolar lavage eosinophilia in a mouse model of bronchial asthma

Allergens, in combination with genetic predisposition, drive undifferentiat ed T cells towards the type 2 T cells. Some childhood infections may activa te the production of a type I T cell profile. It is reasonable to speculate that a decrease in childhood infections may increase the incidence of alle rgy 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 (BC G) vaccine and Mycobacterium vaccae, on antigen-induced bronchoconstriction , airway hyperresponsiveness to methacholine, bronchoalveolar lavage eosino philia, 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. v accae. 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. vac cae 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 I response to BCG. Thes e data support our hypothesis and suggest that BCG and M. vaccae may preven t the underlying pathophysiological changes in asthma. (C) 2001 Elsevier Sc ience B.V. All rights reserved.