Dose-dependent effects of endotoxins on allergen sensitization and challenge in the mouse

Background Levels of endotoxins greatly differ according to environmental settings. Objective To study the effect of lipopolysaccharide (LPS) at increasing doses (0.1-1000 ng) on allergen sensitization and challenge in the mouse. Methods Mice were sensitized systemically and challenged locally with ovalbumin (OVA) in the presence or absence of LPS. Inflammation was assessed by determining total and differential cell counts and T-helper type 2 (Th)2 cytokine (IL-4 and IL-5) levels in bronchoalveolar lavage fluid (BALF). Total and OVA-specific IgE levels were quantified in serum. Airway hyper-responsiveness (AHR) was assessed by whole-body barometric plethysmography. Results Administered prior to sensitization, LPS at 100 or 1000 ng dose-dependently decreased allergen- induced total and OVA-specific IgE, airway eosinophilia and Th2 cytokines in BALF, without changing AHR. Administered during OVA challenge, LPS at 1 ng (an infra-clinical dose) or 100 ng (a dose triggering neutrophilia) enhanced airway eosinophilia, without affecting IgE levels or AHR. Conclusion Our data clearly demonstrate that exposure to LPS influences allergen-induced IgE production and airway eosinophilia in a time and dose-dependent manner, preventing IgE production and development of eosinophilia when administered during allergen sensitization at high doses, and inducing exacerbation of eosinophilia when administered upon allergen challenge at low doses, including infra-clinical doses.