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.

Nitrogen dioxide: no influence on allergic sensitization in an intranasal mouse model with ovalbumin and diesel exhaust particles.

The role of traffic-related air pollution in the development of allergic diseases is still unclear. We therefore investigated if NO2, an important constituent of traffic-related air pollution, promotes allergic sensitization to the allergen ovalbumin (OVA). We also examined if NO2 influenced the allergy adjuvant activity of diesel exhaust particles (DEP). For this purpose, mice were exposed intranasally to OVA with or without DEP present, immediately followed by exposure to NO2 (5 or 25 parts per million [ppm]) or room air for 4 h in whole body exposure chambers. Eighteen hours after the last of three exposures, the lungs of half of the animals were lavaged with saline and markers of lung damage and lung inflammation in the bronchoalveolar lavage fluid (BALF) were measured. Three weeks later, after intranasal booster immunizations with OVA, the levels of OVA-specific IgE and IgG2a antibodies in serum were determined. Both NO2 (25 ppm) and DEP gave lung damage, measured as increased total protein concentration in BALF, whereas only NO2 seemed to stimulate release of the proinflammatory cytokine tumor necrosis factor alpha (TNF-α). In contrast, only DEP significantly increased the number of neutrophils. Furthermore, DEP in combination with OVA stimulated the production of serum allergen-specific IgE antibodies. NO2, however, neither increased the production of allergen-specific IgE antibodies, nor influenced the IgE adjuvant activity of DEP. Thus, based on our findings, NO2 seems to be of less importance than combustion particles in the development of allergic diseases after exposure to traffic-related air pollution.