OZONE-INDUCED IMPAIRMENT OF PULMONARY TYPE IV HYPERSENSITIVITY AND AIRWAY HYPERRESPONSIVENESS IN MICE

Abstract

It is evident that exposure to ozone has toxic effects and can lead to lung function disturbances. Individuals suffering from COPD or asthma are groups especially at risk with respect to the effects of ozone. The majority of studies dealing with ozone effects on pulmonary allergy are restricted to immunoglobulin E (IgE) mediated allergy (type I allergy). It has been demonstrated that ozone can potentiate the induction as well as the effector phase of allergic asthma. Recently it has been demonstrated in animal models that in nonIgE-mediated "asthma," T cells may play a role also. It has been demonstrated in mice that low-molecular-weight compounds can induce pulmonary delayed-type hypersensitivitylike reactions that are Th-1 dependent. For this reason it might be suggested that in certain non-IgE-mediated pulmonary diseases Th-1 cells are involved. This in contrast to the classical allergic immune response in asthma where Th-2 cells are thought to be crucial. Effects of ozone on non-IgE-mediated pulmonary allergy induced by, for example, lowmolecular-weight compounds such as toluene diisocyanate, nickel, and trimellitic anhydride have never been studied. In this study we demonstrated that acute ozone exposure can inhibit pulmonary delayed-type hypersensitivity induced by low-molecular-weight compounds in the mouse. The inflammatory component and the hyperresponsiveness of the trachea that is induced by this type of hypersensitivity reaction are significantly inhibited by ambient ozone levels. As is true for the effects on type I allergy, this type of hypersensitivity can also be affected in the induction as well as the effector phase. The results of this study are in general opposite to the effect on type I allergic reactions. The effect, that is, suppression of type IV hypersensitivity, may be due to activation of Th-2 celldependent reactions that may be potentiated by ozone. This potentiation might lead to a downregulation of Th-1-mediated immunity because Th-1 and Th-2 cells modulate each other's activity. On the other hand, it can also be suggested that ozone has a direct effect on Th-1 cells or other cell types that are crucial for delayed-type hypersensitivity and related airway hyperresponsiveness in this animal model.