Exposure to endotoxin and allergen in early life and its effect on allergen sensitization in mice.
BACKGROUND
Exposure to endotoxins, allergens, or both in early life might regulate the development of tolerance to allergens later in life.


OBJECTIVE
We investigated whether continuous exposure of infant mice to aerosolized endotoxin, allergen, or both inhibits subsequent allergen-induced immune and inflammatory responses.


METHODS
Infant BALB/c mice were pre-exposed to aerosolized endotoxin, ovalbumin (OVA), or both (3 times a week for the first 4 weeks of life) before systemic sensitization (days 1-14) and repeated airway challenge (days 28-30) with OVA.


RESULTS
Compared with that seen in negative control animals, systemic sensitization and airway allergen challenges induced high serum levels of allergen-specific IgE (0.7 +/- 0.09 vs 0.02 +/- 0.01 OD units), predominant T(H)2-type cytokine production (IL-5 by splenic mononuclear cells in vitro, 1.2 +/- 0.2 vs 0.04 +/- 0.06 ng/mL), airway inflammation (bronchoalveolar lavage fluid leukocytes, 125 +/- 15 vs 64 +/- 7/microL; eosinophils, 28 +/- 5 vs 1 +/- 0/microL) and development of in vivo airway hyperreactivity (maximal enhanced pause, 11 +/- 1.9 vs 4 +/- 0.2). Pre-exposure with LPS before sensitization increased production of specific IgG2a (67 +/- 10 vs 32 +/- 5 U/mL) but failed to prevent T(H)2-mediated immune responses. Pre-exposure with OVA or with OVA plus LPS completely suppressed allergen sensitization, airway inflammation, and development of in vivo airway hyperreactivity; values were similar to those of negative control animals. Inhibition was due to allergen-specific T-cell anergy indicated by omitted allergen-specific T(H)2 and T(H)1 immune responses. In addition, combined exposure to endotoxin and allergen induced a general shift toward an unspecific T(H)1 immune response.


CONCLUSIONS
Exposure with endotoxins before allergen sensitization is not able to induce unresponsiveness but might decrease the susceptibility for sensitization to a variety of common allergens.
Gerhold
Kerstin
K
Department of Pediatric Pneumology and Immunology, University Hospital Charité, Berlin, Germany.
Bluemchen
Katharina
K
Franke
Annabelle
A
Stock
Philippe
P
Hamelmann
Eckard
E
D000336:Aerosols; D000485:Allergens / Q000276:immunology*; D000818:Animals; D000831:Animals, Newborn / Q000276:immunology*; D000917:Antibody Formation / Q000187:drug effects; D001991:Bronchitis / Q000276:immunology; D004334:Drug Administration Schedule; D000939:Epitopes; D007114:Immunization; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000008:administration & dosage*
D000336:Aerosols; D000485:Allergens; D000939:Epitopes; D008070:Lipopolysaccharides; D010047:Ovalbumin