Exposure to endotoxin and allergen in early life and its effect on allergen sensitization in mice

Abstract

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 TH2-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/μL; eosinophils, 28 ± 5 vs 1 ± 0/μL) 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 TH2-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 TH2 and TH1 immune responses. In addition, combined exposure to endotoxin and allergen induced a general shift toward an unspecific TH1 immune response. Conclusion: 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.