Ozone-induced airway hyperresponsiveness is reduced in immature mice

During ozone (O-3) exposure, adult mice decrease their minute ventilation ((V)over dotE). 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 (V)over dotE normalized for body weight ((V)over dotE/g) decreased with increasing age, consistent with the higher metabolic rates of younger animals. O-3 caused a concentration-related decrease in (V)over dotE in mice of all ages, but the response was significantly. less in 2-wk-old than in older mice. The increased baseline (V)over dotE/g and smaller decrements in (V)over dotE 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.