Bronchial responsiveness and inflammation in guinea-pigs exposed to toluene diisocyanate: a study on single and repeated exposure.
The question of whether or not toluene diisocyanate (TDI)-induced airway hyperresponsiveness in the guinea-pig is accompanied by neutrophil influx into bronchoalveolar lavage fluid (BALF) was addressed. Two modes of exposure were studied; (1) acute exposures where animals were exposed to 3 ppm TDI for 1 h and experiments were carried out 30 min, 4 h, 24 h, 48 h and 1 week after the TDI exposures; (2) subacute exposures where animals were exposed to 0.080 and 0.046 ppm TDI for 48 h 1 week, respectively, and experiments were carried out 24 h after the TDI exposures. The changes in airway responsiveness to increasing doses of intravenous acetylcholine (ACh) in anaesthetized and tracheotomized spontaneously breathing guinea-pigs were examined. In order to elucidate the possible relationships of airway responsiveness to cellular infiltration, bronchoalveolar lavage was performed in additional group of guinea-pigs exposed to the same conditions. After acute exposure to 3 ppm TDI, increased bronchial responsiveness was evident within 30 min, lasted 48 h, but had vanished 1 week after the exposure. An influx of neutrophils occurred into the BALF within 1 h after exposure. The influx of neutrophil into BALF lasted 48 h and vanished 1 week after the end of exposure. After 48 h of exposure to TDI at 0.080 ppm, or 0.046 ppm for 1 week, increased bronchial responsiveness was evident 24 h after the end of the both modes of exposure, but no influx of neutrophils was observed into the BALF. It was concluded that even though the neutrophil influx and hyperresponsiveness evolve in the same way after acute exposure to a high concentration of TDI (3 ppm), this is not the case after subchronic exposure to low concentrations of TDI, where a bronchial hyperresponsiveness is observed without detectable neutrophil influx.