THE EFFECT OF ENDOTOXIN INHALATION ON AIRWAY RESPONSIVENESS AND CELLULAR INFLUX IN RATS

Studies in humans suggest that airway inflammation may modulate nonspecific airway responsiveness. We studied in a rat model the effect of the inhalation of endotoxin on the cellular composition of the bronchoalveolar lavage (BAL) fluid and airway responsiveness. The exposure to an aerosol of endotoxin caused a rapid influx of neutrophils in the airways. The neutrophils persisted up to 24 h after exposure. Elastase activity in lavage fluid became detectable 30 min after the endotoxin exposure and peaked 9 h later. The exposure to the endotoxin aerosol was followed 1 to 2 h later by a significant increase in the airway responsiveness to 5-hydroxytryptamine (5HT). However, the increase in responsiveness disappeared, and 9 to 12 h following the end of the exposure a significant decrease in airway 5HT responsiveness was observed at the moment that more than 80% of the cells contained in the BAL fluid were neutrophils. The effect of endotoxin on airway responsiveness and inflammation was dose dependent. We also compared in three different inbred rat strains the effect of endotoxin inhalation. The aerosol exposure induced in all three strains a comparable neutrophil influx in the airways, but only two of the three strains became hyperresponsive to 5HT. We conclude that the inhalation of endotoxin causes a neutrophilic airway inflammation in rats. The relationship between this airway inflammation and airway responsiveness is dependent on the time following the exposure and the animal strain used.