Determinants of experimental allergic responses: interactions between allergen dose, sex and age

The prevalence of allergic diseases is influenced by sex and age. Although mouse models are widely used in allergy research, few experimental studies have examined the interaction effects of sex and age on allergy outcomes. Our aim was to investigate the individual and combined effects of sex and age on allergic sensitization and inflammation in two mouse models: an intraperitoneal (i.p.) and an intranasal (i.n.) sensitization model. We also investigated how the allergen immunization dose interacted with age and sex in the i.p. model. Female and male mice were immunized i.p. or i.n. with ovalbumin when 1, 6 or 20 weeks old. In both models, allergen challenges were performed by i.n. delivery. Serum antibodies, draining lymph node cytokine release and airway inflammatory responses were assessed. In the i.p. model, the antibody and cytokine levels and airway inflammation were highly influenced by immunization dose and age. The responses increased with age when using a low immunization dose, but decreased with age when using a high immunization dose. In the i.n. model, antibody production and airway tissue inflammation increased with age. Female compared with male mice generally developed more pronounced antibody and inflammatory responses. Relative to older mice, juvenile mice had augmented airway inflammation to allergen exposures. The study demonstrates that immunization dose, sex and age are highly influential on allergy outcomes. To better mimic different life stages of human allergic airway disease, murine models, therefore, require careful optimization.