Airway hyperresponsiveness and inflammation induced by toluene diisocyanate in guinea pigs

We examined the changes in airway responsiveness to increasing doses of an acetylcholine aerosol in anesthetized and ventilated guinea pigs 2, 6, or 24 h after exposure to 2 ppm toluene diisocyanate (TDI) or 2 h after exposure to air or 1 ppm TDI. Pulmonary resistance (RL) after the animals inhaled a buffered saline aerosol was used as baseline and was similar for air and TDI groups. The concentration of acetylcholine calculated to cause a 200% increase in RL was significantly lower for animals studied at 2 h (0.68%) or at 6 h (0.77%), but not at 24 h (2.39%), after TDI than for air animals (3.07%). The increase in airway responsiveness in the TDI-exposed animals was associated with histologic changes in the trachea and intrapulmonary airways. Exposure to 2 ppm TDI caused a patchy loss of cilia, shedding of epithelial cells into the airway lumen, and an influx of inflammatory cells into the trachea and other airways. In the lamina propria of the trachea, the concentration of extravascular polymorphonuclear leukocytes (PMN) was 13- to 26-fold greater in animals studied 2 or 6 h after exposure to 2 ppm TDI or at 2 h after 1 ppm TDI than in animals exposed to air. The concentration of PMN in the epithelium was significantly increased only in animals examined 2 h after 2 ppm TDI. Exposure to TDI also caused an influx of eosinophils into the tracheal mucosa. This influx occurred later and was more persistent than the influx of PMN. These results indicate that a single exposure to TDI can cause an increase in airway responsiveness that is associated with epithelial injury and acute airway inflammation.