Ozone-induced airway hyperresponsiveness is reduced in immature mice

Abstract

During ozone (O(3)) exposure, adult mice decrease their minute ventilation (VE). To determine whether there are age-related differences in the ventilatory response to O(3), A/J mice, aged 2, 4, 8, or 12 wk, were exposed to O(3) (0.3-3.0 parts/million for 3 h) in nose-only exposure plethysmographs. Baseline VE normalized for body weight (VE/g) decreased with increasing age, consistent with the higher metabolic rates of younger animals. O(3) caused a concentration-related decrease in VE in mice of all ages, but the response was significantly less in 2-wk-old than in older mice. The increased baseline VE/g and smaller decrements in VE induced by O(3) in immature mice resulted in an inhaled dose of O(3) normalized for body weight that was three to four times higher than in adult mice. O(3) exposure caused a dose-related increase in airway responsiveness in 8- and 12-wk-old mice but did not cause airway hyperresponsiveness at any dose in either 2- or 4-wk-old mice, although higher inhaled doses of O(3) normalized for body weight were delivered to these younger animals. Interleukin-6 and macrophage inflammatory protein-2 levels in bronchoalveolar lavage fluid were also increased in 8-wk-old compared with 2-wk-old mice exposed to O(3). The results suggest that immature mice are less sensitive than adult mice to O(3), at least in terms of the ability of O(3) to induce airway hyperresponsiveness and promote release of certain cytokines.