Effect of long-term exposure to low-level toluene on airway inflammatory response in mice.

Volatile organic compounds are the main substances causing multiple chemical sensitivity reactions in human. Our laboratory has previously showed that the exposure of low-level formaldehyde causes immunogenic and neurogenic inflammatory responses in mice. The aim of the present study was to investigate the effect of long-term, low-level toluene exposure on airway inflammatory responses in mice lung. We exposed female C3H mice to filtered air (0ppm) or 50ppm of toluene for 6h/day on 5days/week for 6 or 12 weeks in the whole body exposure chamber. One day following the last toluene exposure, we collected bronchoalveolar lavage fluid from each mouse and examined cellular infiltration and production of cytokines, chemokines, neurotrophins and substance P by using ELISA method. We found that the number of total cells and macrophages increased significantly in both 6 and 12-week-exposed mice. In addition, the production of interferon-gamma and substance P were decreased significantly and nerve growth factor was not affected in both 6 and 12-week-exposed mice. In contrast, neurotrophin-3 production in bronchoalveolar lavage fluid was significantly increased only in 12-week-exposed mice. Our findings suggest that long-term (12-week) exposure of mice to low-level toluene modulates airway inflammatory response via neurological signaling.