title: Exposure to endotoxins during sensitization prevents further endotoxin-induced exacerbation of airway inflammation in a mouse model of allergic asthma.
abstract: BACKGROUND
  We have shown previously that lipopolysaccharides (LPS) inhibited airway inflammation in allergen-sensitized and challenged mice when administered during sensitization, while exacerbating the inflammation when given upon challenge. We have here investigated the effect of LPS administered during both sensitization and challenge on airway inflammation, as well as on the profile of the T-helper (Th) response to allergen.
  
  
  METHODS
  Mice were sensitized and challenged with ovalbumin (OVA), in the presence or absence of effective doses of LPS, namely 1 mug during sensitization and 1 ng during challenge. Inflammation was assessed by measuring cell counts and cytokine levels in bronchoalveolar lavage fluid (BALF). The profile of the Th response was determined by quantifying OVA-specific IgE and IgG2a in serum and Th1/Th2 cytokines in the culture medium of splenocytes and in BALF.
  
  
  RESULTS
  Allergen-induced airway eosinophilia was increased in mice exposed to LPS during challenge only when compared with controls, whereas it was similarly reduced in animals exposed during sensitization only and during both sensitization and challenge. Mice exposed to LPS during sensitization only or during both sensitization and challenge also displayed a decrease in IgE and an increase in IgG2a, suggesting a switch in the immune response toward the Th1 profile. This was confirmed by quantification of Th1/Th2 cytokines in culture medium of splenocytes and in BALF.
  
  
  CONCLUSIONS
  Our data demonstrate that exposure to endotoxins during sensitization prevents allergen-induced airway inflammation, as well as its exacerbation triggered by further exposure to endotoxins during challenge, while switching the immune response to allergen from a Th2 to a Th1 profile.
authors.affiliation: EA 3771, Inflammation et environnement dans l'asthme, Faculté de Pharmacie, Université Louis Pasteur-Strasbourg I, Illkirch, France.
authors.forename: Carine
authors.initials: C
authors.lastname: Delayre-Orthez
authors.forename: Julien
authors.initials: J
authors.lastname: Becker
authors.forename: Frédéric
authors.initials: F
authors.lastname: de Blay
authors.forename: Nelly
authors.initials: N
authors.lastname: Frossard
authors.forename: Françoise
authors.initials: F
authors.lastname: Pons
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000517:prevention & control*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D002452:Cell Count; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D007114:Immunization / Q000379:methods*; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D008070:Lipopolysaccharides / Q000276:immunology* / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D016207:Cytokines; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D007073:Immunoglobulin E; D010047:Ovalbumin