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

Authors: Arts, Josje H. E.; Jacobs, Erik J.; Kuper, C. Frieke

Source: Inhalation Toxicology, Volume 22, Number 3, February 2010 , pp. 179-191(13)

Publisher: Informa Healthcare

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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

Document Type: Research Article


Affiliations: Toxicology and Applied Pharmacology, TNO Quality of Life, Zeist, The Netherlands

Publication date: February 1, 2010

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