Interaction of environmental chemicals with respiratory sensitization.

The acute effects of the inhalation of air polluting agents have been examined by many research groups in both animal models and human beings. For instance, it is evident that exposure to ozone has toxic effects and can lead to lung function disturbances. For this reason it is likely that individuals suffering from COPD or asthma are groups especially at risk with respect to the effects of ozone. The majority of studies dealing with effects of air pollutants on pulmonary allergy are restricted to IgE mediated allergy (type I allergy). Again for ozone, in animal models for type I allergy it has been demonstrated that exposure can affect the induction as well as the effector phase of this type of hyperimmune reaction (e.g. allergic asthma). Recently it has been demonstration in animal models that non-IgE mediated "asthma' T cells, and notably Th1 cells, may play a crucial role. In a murine model it was demonstrated that low molecular weight compounds can induce delayed type hypersensitivity-like reactions in the respiratory tract, and that these reactions are associated with the induction of airway hyperreactivity. Such compounds include toluene diisocyanate (TDI), to which immune responses can be readily mounted, and which can cause occupational asthma through its sensitizing capability, but to which IgE is only detected in a minority of patients suffering from TDI-associated asthma. Effects of air pollutants on Th1 responses in the respiratory tract have not been studied so far. We have demonstrated that ozone can inhibit resistance to a an intratracheal challenge with Listeria monocytogenes, indicating suppression of Th1 immune responses. In addition, we have shown that ozone exposure suppresses pulmonary delayed type hypersensitivity induced by small molecular weight compounds, as well as the tracheal hyperreactivity that is induced during the development of these immune responses, again supporting the hypothesis of suppression of Th1 responses by ozone exposure. These phenomena may be due to activation of Th2 cell dependent reactions that in turn lead to a downregulation of Th1 mediated immunity, or to a direct effect on Th1 cells or other cell types that are crucial for delayed type hypersensitivity and related airway hyperresponsiveness in this model. These data indicate that exposure to air pollutants may have differential consequences on different types of immune responses in the respiratory tract.