title: 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 (SO(2)) 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 SO(2), and challenged by inhalation to a distinctly irritating or minimally irritating concentration of TMA after the (last) SO(2) 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 SO(2) exposure. Repeated pre-exposure to SO(2) reduced the number of TMA-induced apnoeas, in an SO(2) exposure duration-dependent manner. This effect of SO(2) 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 SO(2)-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, SO(2) appeared to facilitate TMA-induced irritation, probably due to incomplete protection. Overall, SO(2) exposure of TMA-sensitized rats reduced TMA-related allergic respiratory responses in most animals.
authors.affiliation: Toxicology and Applied Pharmacology, TNO Quality of Life, Zeist, The Netherlands.
authors.forename: Josje H E
authors.initials: JH
authors.lastname: Arts
authors.forename: Erik J
authors.initials: EJ
authors.lastname: Jacobs
authors.forename: C Frieke
authors.initials: CF
authors.lastname: Kuper
mesh_terms: D000395:Air Pollutants, Occupational / Q000633:toxicity*; D000818:Animals; D001273:Atmosphere Exposure Chambers; D001835:Body Weight / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D005260:Female; D007073:Immunoglobulin E / Q000032:analysis / Q000096:biosynthesis; D007509:Irritants; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D007830:Larynx / Q000473:pathology; D008168:Lung / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D010796:Phthalic Anhydrides; D051381:Rats; D011914:Rats, Inbred BN; D012129:Respiratory Function Tests; D012130:Respiratory Hypersensitivity / Q000517:prevention & control*; D013458:Sulfur Dioxide / Q000633:toxicity*; D014132:Trachea / Q000473:pathology
chemical_list: D000395:Air Pollutants, Occupational; D007509:Irritants; D010796:Phthalic Anhydrides; D013458:Sulfur Dioxide; D007073:Immunoglobulin E; C015559:trimellitic anhydride; D007770:L-Lactate Dehydrogenase