title: Effects of Mycobacterium bovis BCG on the development of allergic inflammation and bronchial hyperresponsiveness in hyper-IgE BP2 mice vaccinated as newborns.
abstract: Asthma may result from excessive Th-2 response in children not previously exposed to Th-1-inducing infections. We tested the hypothesis that BCG vaccination in Th-2-susceptible newborn BP2 mice blocks allergic inflammation and 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 sensitized with 100 microg ovalbumin (OVA) in aluminium hydroxide twice subcutaneously (SC) at 1 week interval, and challenged 1 week after the second sensitization with 10 microg OVA IN. Compared to OVA-challenged unvaccinated mice, those that received BCG 8 weeks before challenge developed intense bronchial inflammation, BHR, and high IgE titers. Inflammation involved T cells, macrophages, dendritic cells and was accompanied by increased levels of Interleukin-5 (IL-5) in the bronchoalveolar lavages (BAL). However, animals challenged 16 weeks after BCG vaccination did not develop BHR nor bronchial hypereosinophilia, and showed reduced IgE levels. Bronchial infiltration by immunocompetent cells was also significantly reduced. Increased levels of gamma-interferon (IFN-gamma) after in vitro stimulation of tracheo-bronchial lymph node cells accompanied this blockage, but levels of IL-5 remained high. We demonstrate that 16 weeks after vaccination with BCG in newborn BP2 mice which have a high Th-2 background, allergic inflammation and BHR were blocked, even though a clear Th-1 shift was not achieved.
authors.affiliation: Unité de Pharmacologie Cellulaire, Unité Associée Institut Pasteur-INSERM U485, Institut Pasteur 25 rue Docteur Roux 75015, Paris, France.
authors.forename: M A
authors.initials: MA
authors.lastname: Nahori
authors.forename: M
authors.initials: M
authors.lastname: Lagranderie
authors.forename: J
authors.initials: J
authors.lastname: Lefort
authors.forename: F
authors.initials: F
authors.lastname: Thouron
authors.forename: D
authors.initials: D
authors.lastname: Joseph
authors.forename: N
authors.initials: N
authors.lastname: Winter
authors.forename: B
authors.initials: B
authors.lastname: Gicquel
authors.forename: J R
authors.initials: JR
authors.lastname: Lapa e Silva
authors.forename: B B
authors.initials: BB
authors.lastname: Vargaftig
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001249:Asthma / Q000517:prevention & control; D001500:BCG Vaccine / Q000008:administration & dosage / Q000494:pharmacology*; D016535:Bronchial Hyperreactivity / Q000517:prevention & control*; D002648:Child; D016207:Cytokines / Q000096:biosynthesis; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D006967:Hypersensitivity / Q000517:prevention & control*; D006968:Hypersensitivity, Delayed; D006969:Hypersensitivity, Immediate; D007249:Inflammation / Q000517:prevention & control*; D007589:Job Syndrome / Q000276:immunology / Q000628:therapy; D008168:Lung / Q000166:cytology / Q000276:immunology; D008297:Male; D051379:Mice; D009163:Mycobacterium bovis / Q000302:isolation & purification; D010047:Ovalbumin / Q000276:immunology; D010641:Phenotype; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D013997:Time Factors
chemical_list: D001500:BCG Vaccine; D016207:Cytokines; D010047:Ovalbumin