Effects of Mycobacterium bovis BCG on the development of allergic inflammation and bronchial hyperresponsiveness in hyper-IgE BP2 mice vaccinated as newborns
Ma. Nahori et al., Effects of Mycobacterium bovis BCG on the development of allergic inflammation and bronchial hyperresponsiveness in hyper-IgE BP2 mice vaccinated as newborns, VACCINE, 19(11-12), 2001, pp. 1484-1495
Asthma may result from excessive Th-2 response in children not previously e
xposed to Th-l-inducing infections. We tested the hypothesis that BCG vacci
nation in Th-2-susceptible newborn BP2 mice blocks allergic inflammation an
d bronchial hyperreactivity (BHR). Ten day-old BP2 mice received 10(5) CFU
of BCG 1173P2 intranasally (IN), and 6, 10 or 14 weeks thereafter were sens
itized with 100 mug ovalbumin (OVA) in aluminium hydroxide twice subcutaneo
usly (SC) at 1 week interval, and challenged 1 week after the second sensit
ization with 10 mug OVA IN. Compared to OVA-challenged unvaccinated mice, t
hose that received BCG 8 weeks before challenge developed intense bronchial
inflammation, BHR, and high IgE titers. Inflammation involved T cells, mac
rophages, dendritic cells and was accompanied by increased levels of Interl
eukin-5 (IL-5) in the bronchoalveolar lavages (BAL). However, animals chall
enged 16 weeks after BCG vaccination did not develop BHR nor bronchial hype
reosinophilia, and showed reduced IgE levels. Bronchial infiltration by imm
unocompetent cells was also significantly reduced. Increased levels of gamm
a-interferon (IFN-gamma) after in vitro stimulation of tracheo-bronchial ly
mph node cells accompanied this blockage, but levels of IL-5 remained high.
We demonstrate that 16 weeks after vaccination with BCG in newborn BP2 mic
e which have a high Th-2 background, allergic inflammation and BHR were blo
cked, even though a clear Th-l shift was not achieved. (C) 2001 Elsevier Sc
ience Ltd. All rights reserved.