Pre-exposure to sulfur dioxide attenuates most allergic reactions upon trimellitic anhydride challenge in sensitized Brown Norway rats

Irritant-induced inflammation of the airways may aggravate respiratory allergy induced by chemical respiratory allergens. Therefore, it was studied whether airway irritation by sulfur dioxide (SO₂) would enhance respiratory allergic reactions to trimellitic anhydride (TMA), using a rat model. Brown Norway (BN) rats were topically sensitized, subsequently exposed for a single time or repeatedly to 300ppm SO₂, and challenged by inhalation to a distinctly irritating or minimally irritating concentration of TMA after the (last) SO₂ exposure. Repeated exposure to SO ₂ alone reduced breathing frequency during exposure, and caused epithelial alterations including hyperplasia and squamous metaplasia, and infiltration of polymorphonuclear inflammatory cells into nasal tissues, larynx, trachea, and bronchi/bronchioli. Histopathological changes were less prominent after 1 day of SO₂ exposure. Repeated pre-exposure to SO₂ reduced the number of TMA-induced apnoeas, in an SO₂ exposure duration-dependent manner. This effect of SO₂ on TMA-induced functional allergic reactions (apnoeas) was distinct only when the TMA challenge concentration was not too irritating itself. Repeated pre-exposure to SO ₂ reduced TMA-induced laryngeal ulceration, goblet-cell hyperplasia, and inflammation in the lungs in most animals, regardless of the TMA challenge concentration. The SO₂-induced replacement of normal respiratory epithelium by less sensitive, squamous epithelium may offer an explanation for the, unexpected, reduced allergic manifestation. However in a few animals, SO₂ appeared to facilitate TMA-induced irritation, probably due to incomplete protection. Overall, SO₂ exposure of TMA-sensitized rats reduced TMA-related allergic respiratory responses in most animals.