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

Abstract

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 300 ppm SO₂, and challenged by inhalation to a distinctly irritating or minimally irritating concentration of TMA after the (last) SO₂ exposure. Repeated exposure to SO₂ 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 SO₂ 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.

Keywords::

• Brown Norway rats
• respiratory allergy
• respiratory irritation
• sulfur dioxide
• trimellitic anhydride

Acknowledgements

They also thank Dr. N. Bloksma for valuable advice on study design, F. Hendriksma, G. Roverts, E. Duistermaat, M. Schijf, J. van Triel, and E. Klein Koerkamp for expert technical assistance, and Dr. H. Muijser for help with the statistical analyses and critically reading the article.

Declaration of interest

The authors gratefully acknowledge CEFIC-LRI Brussels, Belgium, and the Dutch Ministry of Social Affairs and Employment for financial support. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.