title: Pulmonary endotoxin tolerance protects against cockroach allergen-induced asthma-like inflammation in a mouse model.
abstract: BACKGROUND
  Compounds which activate the innate immune system, such as lipopolysaccharide, are significant components of ambient air, and extremely difficult to remove from the environment. It is currently unclear how prior inhalation of endotoxin affects allergen sensitization. We examined whether lung-specific endotoxin tolerance induction prior to sensitization can modulate the response to allergen.
  
  
  METHODS
  Endotoxin tolerance was induced by repeated intratracheal exposure to endotoxin. All mice were then sensitized and challenged by direct intratracheal instillation of cockroach allergen.
  
  
  RESULTS
  After allergen sensitization and challenge, endotoxin tolerant mice had significantly decreased airways hyperresponsiveness to methacholine challenge, which was confirmed by invasive lung function tests. Decreased goblet cell hyperplasia and mucus production were also found by histological assessment. Tolerant mice were protected from airway eosinophilia through the mechanism of reduced CCL11 and CCL24. Interestingly, endotoxin tolerant mice had only a modest reduction in cockroach-specific IgE; however, total IgE was significantly reduced.
  
  
  CONCLUSIONS
  These data show that induction of endotoxin tolerance prior to sensitization protects against the hallmark features of asthma-like inflammation, and that transient modulation of innate immunity can have long-lasting effects on adaptive responses.
authors.affiliation: Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Sudha
authors.initials: S
authors.lastname: Natarajan
authors.forename: Jiyoun
authors.initials: J
authors.lastname: Kim
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Bouchard
authors.forename: William
authors.initials: W
authors.lastname: Cruikshank
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Remick
mesh_terms: D000403:Airway Resistance; D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000517:prevention & control*; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000517:prevention & control; D054413:Chemokine CCL11 / Q000096:biosynthesis; D054423:Chemokine CCL24 / Q000096:biosynthesis; D003058:Cockroaches / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology; D005260:Female; D007108:Immune Tolerance; D007114:Immunization; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000276:immunology; D019476:Insect Proteins / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000276:immunology
chemical_list: D000485:Allergens; C515457:Ccl11 protein, mouse; C515485:Ccl24 protein, mouse; D054413:Chemokine CCL11; D054423:Chemokine CCL24; D016207:Cytokines; D019476:Insect Proteins; D008070:Lipopolysaccharides; D007073:Immunoglobulin E