No abstract

Exposure to chlorine gas (Cl2) causes occupational asthma that we hypothesized occurs through the induction of airway inflammation and airway hyperresponsiveness by oxidative damage. Respiratory mechanics and airway responsiveness to methacholine were assessed in A/J mice 24 hours after a 5-minute exposure to 100, 200, 400, or 800 ppm Cl2 and 2 and 7 days after inhalation of 400 ppm Cl2. Airway responsiveness was higher 24 hours after 400 and 800 ppm Cl2. Responsiveness after inhalation of 400 ppm Cl2 returned to normal by 2 days but was again elevated at 7 days. Airway epithelial loss, patchy alveolar damage, proteinaceous exudates, and inflammatory cells within alveolar walls were observed in animals exposed to 800 ppm Cl2. Macrophages, granulocytes, epithelial cells, and nitrate/nitrite levels increased in lung lavage fluid. Increased inducible nitric oxide synthase expression and oxidation of lung proteins were observed. Epithelial cells and alveolar macrophages from mice exposed to 800 ppm Cl2 stained for 3-nitrotyrosine residues. Inhibition of inducible nitric oxide synthase with 1400W (1 mg/kg) abrogated the Cl2-induced changes in responsiveness. We conclude that chlorine exposure causes functional and pathological changes in the airways associated with oxidative stress. Inducible nitric oxide synthase is involved in the induction of changes in responsiveness to methacholine.

Heaves in horses shares many similarities with human asthma, including lower airway inflammation, reversible airway obstruction, and bronchial hyperresponsiveness. Extrinsic asthma is an allergic response to environmental allergens and a similar immunologic mechanism may be implicated in heaves. It is now recognized that a Th2 subset of CD4+ lymphocytes is associated with allergic diseases such as atopic asthma. The purpose of this study was to determine whether airway inflammation in heaves is associated with a pattern of expression of cytokine suggestive of a Th2 type response. The expression of mRNA, encoding interleukin (IL)-4, IL-5, and interferon gamma (IFN-gamma) was measured in bronchoalveolar cells from seven horses with heaves and five control horses, using in situ hybridization and radiolabeled equine-specific cRNA probes coding for these cytokines. Bronchoalveolar cells of horses with heaves had an increased expression of IL-4 (p = 0.01) and IL-5 (p = 0.02) mRNA and a decreased expression of INF-gamma (p = 0.01) compared with control horses. Here we show that inflammatory cells in lungs from horses with heaves display a Th2-type cytokine profile that is consistent with the hypothesis that heaves is an allergic condition with similarity to human asthma.